NM_007294.3:c.1568T>G (p.Leu523Trp) is a missense variant in BRCA1 exon 10, located outside the clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857).¹ This variant is absent from gnomAD v2.1 (non-cancer exome subset) and present at extremely low frequency in gnomAD v4.1 (1/1,613,758 alleles; AF = 6.20e-7). The absence from the v2.1 outbred population controls meets ENIGMA PM2_Supporting.² The variant falls within the BRCA1 exon 11 coldspot region (aa 224-1366), where no pathogenic missense variants have been observed in ClinVar. Combined with its location outside clinically important functional domains and absence of predicted splicing impact (SpliceAI = 0.00), this meets ENIGMA BP1_Strong.³ In silico predictors are discordant: BayesDel (0.322, ≥0.28 threshold) predicts a damaging protein change but PP3 is not triggered because the variant lies outside clinically important functional domains per ENIGMA rules. REVEL score is 0.613.⁴ No functional data (PS3/BS3), segregation data (PP1/BS4), clinical-history likelihood ratios (PP4/BP5), or case-control studies (PS4) are available for this variant. It is absent from the ENIGMA Table 9 curated functional assay results and from the ST4 functional assay dataset.⁵ The variant is reported in ClinVar as Uncertain significance by 6 clinical laboratories and Likely benign by 1 laboratory (ClinVar ID 54295). No expert panel classification is available.⁶ With PM2_Supporting on the pathogenic side and BP1_Strong on the benign side, the evidence is conflicting and does not meet ENIGMA Table 3 thresholds for Likely Pathogenic, Likely Benign, or Benign classification. The variant remains classified as Uncertain Significance.⁷