NM_016507.4:c.4099G>A (p.Val1367Ile) in CDK12 meets PM2 at supporting level: absent from gnomAD v2.1 and gnomAD-Canada, and present at extremely low frequency in gnomAD v4.1 (1/1,614,182 alleles, AF=6.2×10⁻⁷).¹ BP4 is met at supporting level: multiple computational tools consistently predict a benign effect, including REVEL 0.092, BayesDel −0.587, and SpliceAI max delta 0.02.² PVS1 is not applicable (missense substitution). All other assessed criteria (PS1–PS5, PM1, PM5–PM6, PP1–PP5, BA1, BS1–BS4, BP1–BP2, BP5–BP7) are not met due to absence of variant-specific clinical, functional, segregation, or de novo evidence.³ One supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are present. Under generic ACMG/AMP 2015 combination rules, this yields conflicting evidence — insufficient to classify as pathogenic, likely pathogenic, likely benign, or benign. The overall classification is Variant of Uncertain Significance (VUS).⁴