Variants of uncertain significance (VUS) are the most frequent outcome in germline genetic testing, with almost 30% of patients receiving only VUS results. This delays clinical decisions and forces manual review, complicating the interpretation of rare alleles.
As genomic testing expands, rare variant discovery outpaces clinical curation. Because automated classifiers resolve only some VUS variants, scalable resolution requires systematic integration of diverse data sources. At ESHG 2026 in Gothenburg, we presented an analysis of the performance of VarSome's automated germline classifier (v13.15.2) which integrates evidence from 150+ genomic databases, literature, and community contributions in reclassifying ClinVar VUS variants.