UshEffect-3D: Structure-informed Classification of USH2A Missense Variants for Inherited Retinal Disease (opens in new tab)

Variants of uncertain significance (VUS) in USH2A represent a critical interpretive challenge in inherited retinal disease, with over 70% of ClinVar submissions for this gene currently unresolved. We developed UshEffect-3D, a gene-specific, structure-informed machine learning framework for USH2A missense variant classification. A dataset of 545 curated variants was assembled from ClinVar and LOVD, and AlphaFold2-predicted domain structures were used to generate local structural descriptors co...