NM_133509.4:c.476G>A (p.Arg159His) in RAD51B is classified as Likely benign based on three supporting benign criteria per the generic ACMG/AMP 2015 framework (PMID:25741868). The generic ACMG combination rules require ≥2 supporting benign criteria for Likely benign classification.¹ The variant exceeds the 0.3% BS1 allele frequency threshold in the South Asian subpopulation (gnomAD v2.1 SAS AF = 0.358%, 109/30,430 alleles, 1 homozygote; gnomAD v4.1 SAS AF = 0.337%, 305/90,530 alleles, 3 homozygotes; grpmax FAF = 0.303%), indicating it is too common to be a highly penetrant pathogenic variant (BS1_supporting).² Multiple in silico tools predict a benign impact: REVEL score 0.385 (below 0.5 threshold), BayesDel score 0.129 (near-zero), and SpliceAI max delta 0.00 (no splice impact), meeting BP4_supporting.³ ClinVar reports this variant as Likely benign from three clinical testing laboratories (Ambry Genetics, PreventionGenetics, NHLS; Variation ID 1678949), meeting BP6_supporting.⁴ No pathogenic or likely pathogenic criteria were met. PVS1 does not apply to this missense variant. PS3/PS4 are not met due to absence of variant-specific functional or case-control data. PM2 is not met as the variant frequency exceeds 0.1% in the South Asian population. PP3 is not met because all in silico tools predict a benign effect. PP5 is not met as ClinVar reports Likely benign, not pathogenic.