VarLand: A pipeline to map the structural landscape of missense variants at the proteome scale.

ABSTRACT: Missense variant pathogenicity often arises from disruptions to protein structural features. The integration of large-scale genetic sequencing into clinical workflows, and the availability of accurate artificial intelligence-based protein structure predictions present an opportunity to assess the structure-function relationship of missense variants at a population scale. To harness this potential, we developed VarLand, a computational pipeline that extracts 29 structural and biophysical features from AlphaFold-predicted protein models and nine complementary annotation tools. We applied VarLand to pathogenic missense variants from ClinVar and a population-specific dataset of rare Middle Eastern variants, comparing their feature profiles to high-frequency benign variants from the Genome Aggr

SUBMITTER: Guzman-Vega FJ 

PROVIDER: S-EPMC12816909 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature