ArticleScience (New York, N.Y.)2023
The landscape of tolerated genetic variation in humans and primates.
Open access · greenAbstract readDataset
In one paragraph
Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
51.7field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
115 citing papers in PubMed, 165 citations in OpenAlex.
- PHARMWATCH: A Proposed Multilayer Pharmacogenomics Framework for Contextual Star Allele Interpretation.Clinical and translational science · 2026Article
- The gene-regulatory evolution of the human skeleton.Nature · 2026Article
- A heritability-optimized method for functional prioritization of rare coding variants in complex traits.Nature genetics · 2026Article
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Article
- From conservation scores to language models: a feature engineering perspective on machine learning for genetic variant interpretation.Briefings in bioinformatics · 2026Review
- Rare variant effect estimation and polygenic risk prediction.Nature genetics · 2026Article
- Comparative Genomic Screening Identifies Developmental Constraint Loci Underscoring the Phenotypic Evolution of Syngnathids.Integrative zoology · 2026Article
- Functional Annotation of GWAS Loci Using Public Transcriptome and Epigenome Datasets Reveals Non-Coding Genes and Regulatory Elements Which May Contribute to BMI.International journal of molecular sciences · 2026Article
- Molecular dynamics simulations of intrinsically disordered protein regions enable biophysical interpretation of variant-effect predictors.HGG advances · 2026Article
- Integrating multi-ancestry common and rare variant mapping accelerates therapeutic target discovery.medRxiv : the preprint server for health sciences · 2026Article
- Recessive variants in mitochondrial complex I nuclear subunits are an underrated cause of optic atrophy.Brain : a journal of neurology · 2026Article
- AI in variant analysis: fast track to genetic diagnoses.Human genetics · 2026Review
- Rare protein-coding variation and the genetic architecture of height in >1.4 million individuals.medRxiv : the preprint server for health sciences · 2026Article
- Inference of elevated mutation rates and variant effects using 700k exomes.bioRxiv : the preprint server for biology · 2026Article
- Genomic landscape of drug binding and pharmacogenetic variation across diverse populations using SNPdrug3D.Nature communications · 2026Article
- Functional profiling of 2,193 ASS1 missense variants: Insights into variant pathogenicity and epistatic interactions in citrullinemia type I.PLoS genetics · 2026Article
- Bridging structure and function: artificial intelligence-based modelling of kidney proteins.Nature reviews. Nephrology · 2026Review
- Causal Prediction of TP53 Variant Pathogenicity Using a Perturbation-Informed Protein Language Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Patterns and drivers of 43,617 mosaic chromosomal alterations in blood.Nature genetics · 2026Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
97 authors at 20 institutions in 19 countries.
Hong Gao *Illumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0001-6274-4513
Tobias Hamp *Illumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Jeffrey EdeIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Joshua G SchraiberIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Jeremy McRaeIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0003-3411-9248
Moriel Singer-BerkProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA, 02142, USA.ORCID 0000-0001-8148-0648
Yanshen YangIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Anastasia S D DietrichIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0002-3839-0396
Petko P FizievIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0002-1572-4621
Lukas F K KudernaIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0002-9992-9295
Laksshman SundaramIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0002-8953-3940
Yibing WuIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Aashish AdhikariIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0003-4305-9494
Yair FieldIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0002-5327-1678
Chen ChenIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Serafim BatzoglouIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.
Francois AguetIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0001-9414-300X
Gabrielle LemireProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA, 02142, USA.
Rebecca ReimersDivision of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Daniel BalickDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-6806-1246
Mareike C JaniakSchool of Science, Engineering & Environment, University of Salford, Salford M5 4WT, UK.ORCID 0000-0002-7759-2556
Martin KuhlwilmInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0002-0115-1797
Joseph D OrkinInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0001-6922-2072
Shivakumara ManuAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.ORCID 0000-0002-9114-8793
Alejandro ValenzuelaInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0002-2252-3887
Juraj BergmanBioinformatics Research Centre, Aarhus University, Aarhus 8000, Denmark.ORCID 0000-0002-9415-2747
Marjolaine RousselleBioinformatics Research Centre, Aarhus University, Aarhus 8000, Denmark.ORCID 0000-0003-3930-0732
Felipe Ennes SilvaResearch Group on Primate Biology and Conservation, Mamirauá Institute for Sustainable Development, Estrada da Bexiga 2584, Tefé, Amazonas, CEP 69553-225, Brazil.ORCID 0000-0002-1315-0847
Lidia AguedaCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain.ORCID 0000-0003-3358-2759
Julie BlancCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain.ORCID 0000-0002-5367-0628
Marta GutCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain.ORCID 0000-0002-4063-7159
Dorien de VriesSchool of Science, Engineering & Environment, University of Salford, Salford M5 4WT, UK.ORCID 0000-0002-6809-0052
Ian GoodheadSchool of Science, Engineering & Environment, University of Salford, Salford M5 4WT, UK.ORCID 0000-0002-3110-9442
R Alan HarrisHuman Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.ORCID 0000-0002-7333-4752
Muthuswamy RaveendranHuman Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.ORCID 0000-0001-6185-4059
Axel JensenDepartment of Ecology and Genetics, Animal Ecology, Uppsala University, SE-75236 Uppsala, Sweden.ORCID 0000-0003-1766-560X
Idriss S ChumaTanzania National Parks, Arusha, Tanzania.ORCID 0000-0001-6622-8321
Julie E HorvathNorth Carolina Museum of Natural Sciences, Raleigh, NC 27601, USA.ORCID 0000-0002-6426-035X
Christina HvilsomCopenhagen Zoo, 2000 Frederiksberg, Denmark.ORCID 0000-0001-7870-6888
David JuanInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0003-1912-9667
Peter FrandsenCopenhagen Zoo, 2000 Frederiksberg, Denmark.ORCID 0000-0001-7131-0944
Fabiano R de MeloUniversidade Federal de Viçosa, Viçosa, 36570-900, Brazil.ORCID 0000-0001-9958-2036
Fabrício BertuolUniversidade Federal do Amazonas, Departamento de Genética, Laboratório de Evolução e Genética Animal (LEGAL), Manaus, Amazonas, 69080-900, Brazil.ORCID 0000-0001-6431-6950
Hazel ByrneDepartment of Anthropology, University of Utah, Salt Lake City, UT 84102, USA.ORCID 0000-0002-0351-3181
Iracilda SampaioUniversidade Federal do Para, Guamá, Belém - PA, 66075-110, Brazil.
Izeni FariasUniversidade Federal do Amazonas, Departamento de Genética, Laboratório de Evolução e Genética Animal (LEGAL), Manaus, Amazonas, 69080-900, Brazil.ORCID 0000-0002-1416-4351
João Valsecchi do AmaralResearch Group on Terrestrial Vertebrate Ecology, Mamirauá Institute for Sustainable Development, Tefé, Amazonas, 69553-225, Brazil.ORCID 0000-0002-9138-0381
Mariluce MessiasUniversidade Federal de Rondonia, Porto Velho, Rondônia, 78900-000, Brazil.ORCID 0000-0002-8322-3327
Maria N F da SilvaInstituto Nacional de Pesquisas da Amazonia, Petrópolis, Manaus - AM, 69067-375, Brazil.ORCID 0000-0001-7613-8004
Mihir TrivediLaboratory for the Conservation of Endangered Species, CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India.
Rogerio RossiUniversidade Federal do Mato Grosso, Boa Esperança, Cuiabá - MT, 78060-900, Brazil.ORCID 0000-0003-2353-5000
Tomas HrbekUniversidade Federal do Amazonas, Departamento de Genética, Laboratório de Evolução e Genética Animal (LEGAL), Manaus, Amazonas, 69080-900, Brazil.ORCID 0000-0003-3239-7068
Nicole AndriaholinirinaLife Sciences and Environment, Technology and Environment of Mahajanga, University of Mahajanga, Mahajanga, 401, Madagascar.
Clément J RabarivolaLife Sciences and Environment, Technology and Environment of Mahajanga, University of Mahajanga, Mahajanga, 401, Madagascar.
Alphonse ZaramodyLife Sciences and Environment, Technology and Environment of Mahajanga, University of Mahajanga, Mahajanga, 401, Madagascar.
Clifford J JollyNew York University, New York City, NY 10012, USA.
Jane Phillips-ConroyWashington University in St. Louis, St. Louis, MO 63130, USA.ORCID 0000-0002-8987-3419
Gregory WilkersonKeeling Center for Comparative Medicine and Research, MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3773-1064
Christian AbeeKeeling Center for Comparative Medicine and Research, MD Anderson Cancer Center, Houston, TX 77030, USA.
Joe H SimmonsKeeling Center for Comparative Medicine and Research, MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-1815-6831
Eduardo Fernandez-DuqueYale University, New Haven, CT 06520, USA.ORCID 0000-0002-3993-7912
Sree KanthaswamyArizona State University, Tempe, AZ 85281, USA.
Fekadu ShiferawGuinea Worm Eradication Program, The Carter Center Ethiopia, PoB 16316, Addis Ababa 1000, Ethiopia.
Dongdong WuState Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.ORCID 0000-0001-7101-7297
Long ZhouCenter for Evolutionary & Organismal Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.ORCID 0000-0001-7596-2691
Yong ShaoState Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.ORCID 0000-0003-1704-8425
Guojie ZhangCenter for Evolutionary & Organismal Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.ORCID 0000-0001-6860-1521
Julius D KeyyuTanzania Wildlife Research Institute (TAWIRI), Head Office, P.O. Box 661, Arusha, Tanzania.ORCID 0000-0002-6888-4987
Sascha KnaufInstitute of International Animal Health/One Health, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald - Insei Riems, Germany.ORCID 0000-0001-5744-4946
Minh D LeDepartment of Environmental Ecology, Faculty of Environmental Sciences, University of Science and Central Institute for Natural Resources and Environmental Studies, Vietnam National University, Hanoi 100000, Vietnam.ORCID 0000-0002-2953-2815
Esther LizanoInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0003-3304-9807
Stefan MerkerDepartment of Zoology, State Museum of Natural History Stuttgart, 70191 Stuttgart, Germany.ORCID 0000-0003-3142-7720
Arcadi NavarroInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0003-2162-8246
Thomas BataillonBioinformatics Research Centre, Aarhus University, Aarhus 8000, Denmark.ORCID 0000-0002-4730-2538
Tilo NadlerCuc Phuong Commune, Nho Quan District, Ninh Binh Province 430000, Vietnam.
Chiea Chuen KhorGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore 138672, Republic of Singapore.
Jessica LeeMandai Nature, 80 Mandai Lake Road, Singapore 729826, Republic of Singapore.ORCID 0000-0003-0757-4237
Patrick TanGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore 138672, Republic of Singapore.ORCID 0000-0002-0179-8048
Weng Khong LimSingHealth Duke-NUS Institute of Precision Medicine (PRISM), Singapore 168582, Republic of Singapore.ORCID 0000-0003-4391-1130
Andrew C KitchenerDepartment of Natural Sciences, National Museums Scotland, Chambers Street, Edinburgh EH1 1JF, UK.ORCID 0000-0003-2594-0827
Dietmar ZinnerCognitive Ethology Laboratory, Germany Primate Center, Leibniz Institute for Primate Research, 37077 Göttingen, Germany.ORCID 0000-0003-3967-8014
Ivo GutCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain.ORCID 0000-0001-7219-632X
Amanda MelinDepartment of Anthropology & Archaeology, University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.ORCID 0000-0002-0612-2514
Katerina GuschanskiDepartment of Ecology and Genetics, Animal Ecology, Uppsala University, SE-75236 Uppsala, Sweden.ORCID 0000-0002-8493-5457
Mikkel Heide SchierupBioinformatics Research Centre, Aarhus University, Aarhus 8000, Denmark.ORCID 0000-0002-5028-1790
Robin M D BeckSchool of Science, Engineering & Environment, University of Salford, Salford M5 4WT, UK.ORCID 0000-0002-7050-7072
Govindhaswamy UmapathyAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.ORCID 0000-0003-4086-7445
Christian RoosGene Bank of Primates and Primate Genetics Laboratory, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany.ORCID 0000-0003-0190-4266
Jean P BoubliSchool of Science, Engineering & Environment, University of Salford, Salford M5 4WT, UK.ORCID 0000-0002-5833-9264
Monkol LekDepartment of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.
Shamil SunyaevDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0001-5715-5677
Anne O'Donnell-LuriaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA, 02142, USA.ORCID 0000-0001-6418-9592
Heidi L RehmProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA, 02142, USA.ORCID 0000-0002-6025-0015
Jinbo XuIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0001-7111-4839
Jeffrey RogersHuman Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.ORCID 0000-0002-7374-6490
Tomas Marques-BonetInstitute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.ORCID 0000-0002-5597-3075
Kyle Kai-How FarhIllumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.ORCID 0000-0001-6947-8537
Illumina (United States) · USUniversity of Salford · GBAarhus University · DKBroad Institute · USBaylor College of Medicine · USCentre for Cellular and Molecular Biology · INCentre for Genomic Regulation · ESInstitut de Biologia Evolutiva · ESThe University of Texas MD Anderson Cancer Center · USUniversité de Mahajanga · MGAgency for Science, Technology and Research · SGBrigham and Women's Hospital · USCopenhagen Zoo · DKGerman Primate Center · DEInstitució Catalana de Recerca i Estudis Avançats · ESInstituto Nacional de Pesquisas da Amazônia · BRKunming Institute of Zoology · CNUniversidade Federal do Amazonas · BRUppsala University · SEYale University · US
Funding
Specific Pathogen Free Baboon Research Resource (SPFBRR) - Bridge Funding Administrative SupplementP40OD024628 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WILLIAM D HOPKINS · 2017 to 2026
$15.7MSTATISTICAL DATA ENCLAVE COREP30AG012836 · NIA · UNIVERSITY OF PENNSYLVANIA · PI KOHLER, HANS-PETER · 1999 to 2024
$14.0MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MPopulation Science Research Center Development CoreR24HD044964 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI SMITH, HERBERT L. · 2003 to 2017
$9.8MNew Computational Methods for Data-driven Protein Structure PredictionR01GM089753 · NIGMS · TOYOTA TECHNOLOGICAL INSTITUTE / CHICAGO · PI XU, JINBO · 2010 to 2023
$3.8MNIA NIH HHS P30 AG012836NICHD NIH HHS R24 HD044964NIGMS NIH HHS R01 GM089753NIGMS NIH HHS T32 GM007748NIH HHS P40 OD024628
Abstract
Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
Indexed as
Genetic VariationPrimatesAnimalsBase SequenceGene FrequencyHumansWhole Genome Sequencing
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