NM_133509.4:c.121G>A (p.Val41Met) is a missense variant in RAD51B, a gene in which loss-of-function truncating variants are the established germline disease mechanism for melanoma and breast/ovarian cancer predisposition.¹ This variant is extremely rare in population databases: present at an allele frequency of 6.20e-07 in gnomAD v4.1 (1/1,613,612 alleles) and absent from gnomAD v2.1 and gnomAD-Canada, meeting PM2 at supporting strength.² Multiple in silico predictors are concordant for a benign effect: REVEL score 0.039 (benign), BayesDel score -0.491 (benign), and SpliceAI max delta 0.13 (no splice impact), meeting BP4 at supporting strength.³ As a missense variant in a gene where truncating variants are the primary pathogenic mechanism, BP1 applies at supporting strength. The variant is absent from ClinVar; no functional studies, segregation data, case-control data, or de novo observations are available. No publications specifically mention NM_133509.4:c.121G>A.⁴ With one supporting pathogenic criterion (PM2) and two supporting benign criteria (BP1, BP4), the net evidence is insufficient to classify this variant as either pathogenic or benign. The variant is classified as a Variant of Uncertain Significance (VUS).⁵