NM_133509.4:c.1111C>T is a nonsense variant predicting p.(Gln371Ter) in exon 11 of RAD51B. Loss of function is an established germline disease mechanism for RAD51B, supported by reports of truncating mutations in breast cancer, ovarian cancer, and melanoma families.¹ The premature termination codon is in the last exon where nonsense-mediated decay is not predicted, and only 13 C-terminal amino acids are truncated. Under the ClinGen SVI PVS1 framework (PMC6185798), a nonsense variant in the last exon with established LOF mechanism qualifies for PVS1 at moderate strength.² This variant is present at extremely low frequency in gnomAD v4.1 (AF = 4.53 × 10⁻⁶, 6/1,324,198 alleles, 0 homozygotes) and is absent from gnomAD v2.1 and gnomAD-Canada, satisfying PM2 at supporting strength for a rare disease variant.³ The variant is absent from ClinVar and has not been reported in any published case-control study. No variant-specific functional data or segregation data are available. The C-terminal tail (residues 371–384) has not been functionally characterized.⁴ OncoKB classifies this variant as Likely Oncogenic with a predicted loss-of-function mechanism, consistent with the established role of RAD51B in homologous recombination repair. Gene-level functional studies demonstrate that RAD51B haploinsufficiency causes centrosome fragmentation, aneuploidy, and impaired homologous recombination.⁵ Combined evidence: PVS1_Moderate + PM2_Supporting. No benign criteria are met. Using the ACMG/AMP 2015 combination rules, this classification reaches Likely Pathogenic.⁶