NM_032043.3:c.611C>G (p.Ser204Cys) is a missense variant in BRIP1 that is absent from all large population databases including gnomAD v2.1, v4.1, and gnomAD-Canada.¹ Multiple in silico predictors (REVEL 0.24, BayesDel -0.212, SpliceAI max delta 0.00) indicate this variant is tolerated and does not affect splicing.² No variant-specific functional studies, case-control data, co-segregation data, or de novo observations were identified for this variant in the peer-reviewed literature. Applying generic ACMG/AMP 2015 classification rules (PMID:25741868): one moderate pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, resulting in insufficient evidence for classification; the variant is a Variant of Uncertain Significance (VUS).³