Article

A knowledge-based distance metric highlights underperformance of variant effect predictors on gain-of-function missense variants

2025-07-28

Abstract excerpt

Most current variant effect predictors (VEPs) are less effective at identifying non-loss-of-function (non-LOF) disease variants, which arise due to a gain of function (GOF) or dominant-negative (DN) mechanism. Previously, we showed that Extent of Disease Clustering (EDC), a structure-derived metric, can be used to prioritize putative non-LOF genes due to the tendency of their pathogenic missense variants to cluste...

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Literature Corpus work: 1918b564-5cea-58df-9406-29a9b40f3dbc
DOI: 10.1101/2025.07.23.666325

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