BP1_Strong is met: the missense variant p.Phe81Leu (c.241T>C) lies outside both ENIGMA-defined clinically important functional domains (PALB2 binding domain aa 10-40 and DNA binding domain aa 2481-3186), and SpliceAI predicts no splicing impact (max delta = 0.00).¹ PM2_Supporting is met: the variant is absent from gnomAD v2.1 and v4.1 in outbred, non-cancer populations.² The sister variant c.241T>G (p.Phe81Val) is classified as Likely Benign by Parsons et al. 2019 multifactorial analysis (posterior probability 0.0066, IARC class 2), consistent with the BP1_Strong assignment for this position.³ Katagiri et al. 1998 (PMID:9609997) observed c.241T>C in Family #32, a Japanese breast cancer family with 3 affected individuals (ages 35, 44, 58). The authors noted this was a novel missense alteration but did not perform segregation or functional analysis, and stated such analyses are needed to confirm pathogenicity.⁴ No functional data (PS3/BS3), case-control data (PS4), clinical history LR (PP4/BP5), co-segregation data (PP1/BS4), or proband-level data (BS2) are available for this variant. Under ENIGMA Table 3 combining rules: BP1_Strong (benign) and PM2_Supporting (pathogenic) are conflicting. Likely Benign requires 1 Strong Benign + 1 Supporting Benign; Likely Pathogenic requires substantially more pathogenic evidence. The evidence supports assignment as a Variant of Uncertain Significance (VUS) with conflicting evidence.⁵