PS3_Strong is met: three independent calibrated functional studies (Findlay 2018, Petitalot 2019, Fernandes 2019) demonstrate that p.Gln1811Arg exhibits protein function comparable to pathogenic control variants (ENIGMA Table 9; functional impact complete, IARC class 5).¹ PM2_Supporting is met: the variant is absent from gnomAD v2.1 (non-cancer exomes) and observed at extremely low frequency in gnomAD v4.1 (1/1,614,234 alleles; AF=6.19×10⁻⁷).² PP3 and BP4 are not met: BayesDel no-AF score of 0.192 falls in the intermediate range between the BP4 threshold (≤0.15) and the PP3 threshold (≥0.28) for variants inside the BRCT clinically important domain.³ PP4 and BP5 are not met: the clinical-history likelihood ratio (LR=0.993 from Li et al. 2020, N=3 probands) falls within the neutral zone, neither supporting pathogenicity nor benignity.⁴ PVS1, PM5, and BP1 are not applicable: PVS1 is restricted to null variants; PM5_PTC is N/A for exon E21(22) per ENIGMA Table 4; BP1 requires location outside a clinically important functional domain (Gln1811 is within the BRCT domain).⁵ Under ENIGMA Table 3 combining rules, the evidence profile of one Strong criterion (PS3) plus one Supporting criterion (PM2) is insufficient to classify as Likely Pathogenic (requires ≥2 Strong, or 1 Strong + ≥2 Supporting, or 1 Strong + 1–2 Moderate). The variant is classified as a Variant of Uncertain Significance (VUS).⁶