NM_058216.3:c.30G>T (p.Met10Ile) is a missense variant in exon 1 of RAD51C, a gene associated with autosomal dominant hereditary breast and ovarian cancer and autosomal recessive Fanconi anemia.¹ This variant is present at extremely low frequency in population databases: gnomAD v2.1 (1/251,450 alleles, AF=3.98e-6), gnomAD v4.1 (1/1,614,238 alleles, AF=6.19e-7), and absent from gnomAD-Canada, meeting PM2 at supporting level.² Multiple in silico predictors suggest a benign effect: REVEL score is 0.24 (below the typical pathogenic threshold of 0.5), BayesDel score is -0.112 (consistent with benign), and SpliceAI predicts no splicing impact (max delta=0.04). This meets BP4 at supporting benign level.³ This variant has been reported in ClinVar as Uncertain significance by three clinical laboratories (ClinVar Variation ID: 538784). No expert panel has classified this variant as pathogenic or benign.⁴ The ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel has published a specification document for RAD51C (Version 1.0.0), but the criterion-level rules are not yet structured for automated application. The generic ACMG/AMP 2015 framework was used as fallback.⁵ No variant-specific functional studies, segregation data, de novo reports, or case-control analyses were identified for this exact variant. The comprehensive RAD51C functional screen by Hu et al. 2023 (PMID:37253112) tested 173 missense variants but did not include p.Met10Ile.⁶ With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), the evidence is indeterminate. This variant is classified as a Variant of Uncertain Significance (VUS) under generic ACMG/AMP 2015 combination rules.⁷