Variants of uncertain significance (VUS) in BRCA1/2 remain a persistent challenge for clinical genetics because they complicate genetic counseling and may limit access to targeted therapies. The BRCA2 c.7847C>T (p.Ser2616Phe) variant recurs almost exclusively among Japanese individuals and has been reported as a VUS. Integrating nationwide registry data, clinic-based ascertainment, literature review, and orthogonal functional genomics, the totality of evidence now supports reclassification to likely pathogenic. Carriers present ages at first cancer onset, histopathology, and tumor spectra compatible with BRCA2-associated hereditary breast and ovarian cancer (HBOC). Population resources demonstrate absence from large global datasets and extremely low frequency in Japanese reference panels, consistent with a rare, population-specific variant. Quantitative co-segregation from informative pedigrees was not conclusive due to a limited number of genotyped individuals; however, the evidence becomes more convincing when combined with high-throughput functional assays demonstrating deleterious effects consistent with BRCA2 loss-of-function. According to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, criteria PS3, PM2, and PM3 together with PP3 are met, justifying a likely pathogenic designation. These findings have implications for surveillance, cascade testing, and therapeutic decision-making in Japan.