ArticleHuman mutation2023
REVEL Is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants.
Article in Human mutation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Determining Causality in Gene Discovery: A Nephrologist's Perspective with Insights from ATP6V0A4.Journal of the American Society of Nephrology : JASN · 2026Article
- Review
- Interpreting the effects of DNA polymerase variants at the structural level.Molecular oncology · 2026Article
- Integration of Machine Learning-Based Pathogenicity Prediction and Phenotype Matching Improves Variant Prioritization in Rare Clinical Testing.Current issues in molecular biology · 2026Article
- Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa.medRxiv : the preprint server for health sciences · 2026Article
- A founder variant in TANGO2 p.(Leu148Trp) in ten Palestinian families: clinical characterization and haplotype analysis of TANGO2 deficiency disorder.BMC medical genomics · 2026Article
- The potential of whole genome sequencing in pharmacogenetics: a retrospective health record study in rare disease patients.European journal of human genetics : EJHG · 2026Article
- MAVISp: A modular structure-based framework for protein variant effects.Protein science : a publication of the Protein Society · 2026Article
- Knowledge graph visualization and retrospective analysis of genetic research on pediatric cardiomyopathy (2000-2024).Frontiers in cardiovascular medicine · 2026Article
- 17α-hydroxylase deficiency with a novelTranslational pediatrics · 2025Article
- Advances in Understanding the Molecular Dynamics of Autosomal Dominant Auditory Neuropathy: Unveiling a Novel DIAPH3 Gene Variant Associated With Sensorineural Hearing Loss and Bilateral Vestibular Aqueduct Enlargement.Journal of audiology & otology · 2025Article
- Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.PLoS genetics · 2025Article
- Case Report: Decoding genetic risks of vascular parkinsonism: a case series.Frontiers in genetics · 2025Article
- An unexpected discovery of a novel potentially pathogenic APP gene variant: a case report of slowly progressive Alzheimer's disease with prominent cerebral amyloid angiopathy.Frontiers in neuroscience · 2025Article
- Whole-exome sequencing and Drosophila modelling reveal mutated genes and pathways contributing to human ovarian failure.Reproductive biology and endocrinology : RB&E · 2024Article
- Using computational approaches to enhance the interpretation of missense variants in the PAX6 gene.European journal of human genetics : EJHG · 2024Article
- Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant.Brain : a journal of neurology · 2024Article
- The expanded spectrum of human disease associated with GREB1L likely includes complex congenital heart disease.Prenatal diagnosis · 2024Article
- REVEL Is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants.Human mutation · 2023Article
Corrections and comments
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5 authors.
Funding
Abstract
In silico predictive tools can help determine the pathogenicity of variants. The 2015 American College of Medical Genetics and Genomics (ACMG) guidelines recommended that scores from these tools can be used as supporting evidence of pathogenicity. A subsequent publication by the ClinGen Sequence Variant Interpretation Working Group suggested that high scores from some tools were sufficiently predictive to be used as moderate or strong evidence of pathogenicity. REVEL is a widely used metapredictor that uses the scores of 13 individual in silico tools to calculate the pathogenicity of missense variants. Its ability to predict missense pathogenicity has been assessed extensively; however, no study has previously tested whether its performance is affected by whether the missense variant acts via a loss-of-function (LoF) or gain-of-function (GoF) mechanism. We used a highly curated dataset of 66 confirmed LoF and 65 confirmed GoF variants to evaluate whether this affected the performance of REVEL. 98% of LoF and 100% of GoF variants met the author-recommended REVEL threshold of 0.5 for pathogenicity, while 89% of LoF and 88% of GoF variants exceeded the 0.75 threshold. However, while 55% of LoF variants met the threshold recommended for a REVEL score to count as strong evidence of pathogenicity from the ACMG guidelines (0.932), only 35% of GoF variants met this threshold (
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