ArticleScience (New York, N.Y.)2012
Evolution and functional impact of rare coding variation from deep sequencing of human exomes.
Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,008 papers, 2 of them syntheses that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,008 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Integrated genomic analyses of acral and mucosal melanomas nominate novel driver genes.Genome medicine · 2022Pooled it
- Trans-ethnic meta-analysis of rare variants in sequencing association studies.Biostatistics (Oxford, England) · 2021Pooled it
- Trial
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- Imputation in the Wild: Genome-Wide Robustness and Fine-Scale Limitations of Low-Coverage Genomes in Endangered Species.Molecular ecology resources · 2026Article
- From Nuisance to Signal: Leveraging Close Relatives in Biobank-Scale Demographic Inference.bioRxiv : the preprint server for biology · 2026Article
- Article
- Evaluating confounding in rare variant genome wide association studies.Nature communications · 2026Article
- Mutation Spectrum ofInternational journal of molecular sciences · 2026Article
- Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration.Nature genetics · 2026Article
- A Compound Heterozygous Missense Variant in TheInternational journal of fertility & sterility · 2026Article
- Computing coalescence rates for complex demographies and sampling configurations.bioRxiv : the preprint server for biology · 2026Article
- Inference of population demographic history captures differing evolutionary signals based on the number of individuals in the dataset.bioRxiv : the preprint server for biology · 2026Article
- Identifying Adaptive Footprints in the Presence of Demographic Uncertainty.Genome biology and evolution · 2026Article
- Disordered but Different: Functional and Evolutionary Divergence of Transcription Factor Intrinsically Disordered Regions.bioRxiv : the preprint server for biology · 2026Article
- Article
- Ancestry-specific performance of variant effect predictors in clinical variant classification.bioRxiv : the preprint server for biology · 2026Article
948 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors.
Funding
Abstract
As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111× in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.