NM_007294.4:c.670G>A (p.Ala224Thr) is a missense variant in BRCA1 exon 9(10). This variant is absent from gnomAD v2.1 and present as a singleton in gnomAD v4.1 (1/1,612,828 alleles, AF=6.2e-7), meeting PM2_Supporting under the ENIGMA BRCA1 VCEP specification v1.2.0.1 BP1_Strong is applied: the variant is a missense substitution located at amino acid position 224, which lies outside all three BRCA1 clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857), and SpliceAI predicts no splicing impact (max delta = 0.00).2 BayesDel no-AF score is 0.183, falling in the intermediate zone between BP4 (≤0.15) and PP3 (≥0.28); REVEL score is 0.541. Neither PP3 nor BP4 can be applied.3 The variant-specific clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is 1.76 based on 1 proband, falling in the neutral zone (>0.48 and <2.08). Neither PP4 nor BP5 is applicable.4 No functional assay data (PS3/BS3), case-control data (PS4), co-segregation data (PP1/BS4), or same-residue pathogenic comparator (PS1) was identified for this variant.5 Under the ENIGMA Table 3 combining rules, the evidence consists of BP1_Strong (1 strong benign) and PM2_Supporting (1 supporting pathogenic). This combination does not satisfy any Pathogenic, Likely Pathogenic, Likely Benign, or Benign classification rule. The variant is classified as a Variant of Uncertain Significance (VUS).6