Benchmarking AlphaMissense against ClinVar for Diagnostic Interpretation of Missense Variants in Inherited Retinal Diseases.

ABSTRACT:

Purpose

AlphaMissense is a newer deep learning-based variant predictor that evaluates the structural consequences of missense variants, the most common pathogenic variant type in inherited retinal diseases (IRDs). This study evaluates the diagnostic utility of AlphaMissense in IRDs by assessing its concordance with ClinVar annotations and exploring how other variant-level metrics may refine its predictions.

Design

A cross-sectional benchmarking study using public variant resources, with a single illustrative clinical case.

Participants

Missense variants from 107 IRD genes; 1 patient case undergoing long-read sequencing.

Methods

Pathogenicity scores from AlphaMissense were extracted from 128 248 variants present in both IRD genes and the Genome Aggregation Datab

SUBMITTER: Lindquist M 

PROVIDER: S-EPMC12765323 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature