This variant is absent or extremely rare in large population cohorts: gnomAD v2.1 allele frequency 0.00389% (11/282,764 alleles) and v4.1 allele frequency 0.00229% (37/1,613,586 alleles), meeting PM2 at supporting level.¹ Multiple in silico predictors do not support a deleterious effect: REVEL score 0.089, BayesDel score -0.494, and SpliceAI predicts no splicing impact (max delta 0.04), meeting BP4 at supporting level.² The variant has been reported in ClinVar as Uncertain significance by 4 clinical laboratories and Likely benign by 1 clinical laboratory (ClinVar Variation ID: 898372). No expert panel classification is available.³ The variant is a missense substitution (p.Ala175Val) and does not qualify for PVS1. No functional studies, segregation data, case-control comparisons, or de novo observations were identified for this variant.⁴ Applying generic ACMG/AMP 2015 final combination rules (PMID:25741868): PM2_supporting and BP4_supporting provide conflicting lines of evidence with no other criteria met. The variant is classified as a Variant of Uncertain Significance (VUS).⁵