NM_133509.3:c.481C>T (p.Pro161Ser) is absent from gnomAD v2.1 and v4.1, meeting PM2 at supporting strength.¹ The variant is a missense change in RAD51B, a gene where the established disease mechanism is loss-of-function via truncating variants. Published germline RAD51B pathogenic variants are nonsense or splice-site mutations (PMID:25600502), and systematic screening of RAD51B found no pathogenic missense variants in breast cancer families (PMID:21533530). BP1 is met at supporting benign strength. Multiple in silico tools predict a benign effect: REVEL score 0.289, BayesDel score -0.077, and SpliceAI max delta 0.11. BP4 is met at supporting benign strength.² The variant is absent from ClinVar; no classification or functional evidence exists for this variant in the literature. OncoKB reports unknown oncogenic effect, and COSMIC reports the variant in somatic cancers (n=2) without functional characterization.³ Applying generic ACMG/AMP 2015 combination rules (PMID:25741868): with two supporting benign criteria (BP1, BP4) and one supporting pathogenic criterion (PM2), the evidence weighs in favor of a benign interpretation, meeting the threshold for Likely Benign.⁴