PM2 (supporting) is met: NM_001174067.1:c.475G>A is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 (allele frequency 0%).¹ BP4 (supporting benign) is met: multiple lines of in silico evidence suggest no deleterious impact, including SpliceAI max delta 0.03 (no splicing effect), BayesDel 0.049 (benign range), and REVEL 0.522 (indeterminate).² PVS1 is not applicable: c.475G>A is a missense variant (p.Glu159Lys) and does not meet the null-variant criteria required for PVS1 assessment per ClinGen SVI PVS1 recommendations (PMC6185798).³ PS3/BS3 not assessed: no well-established functional studies were identified for this variant. OncoKB reports Unknown Oncogenic Effect.⁴ PP5/BP6 not assessed: ClinVar submissions were matched to a different variant (NM_023110.3:c.742G>A, p.Val248Met) and all are non-exact matches; no expert panel or reputable source classification exists for this specific variant.⁵ PS4 not met: variant is rare (absent from gnomAD) but no case-control enrichment data are available to establish statistically significant association with disease.⁶ PP3 not met: combined in silico evidence (REVEL 0.522, BayesDel 0.049, SpliceAI max delta 0.03) does not support a deleterious effect.⁷ No publications reviewed (PMIDs: 21082653, 20301509, 20301628, 28492532) mention the specific variant NM_001174067.1:c.475G>A. All are gene-level reviews or methodology papers without variant-specific evidence. Final classification: Uncertain Significance (VUS). One supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, yielding conflicting evidence that does not meet the threshold for Likely Pathogenic, Likely Benign, Pathogenic, or Benign classification under generic ACMG/AMP 2015 combination rules (PMID:25741868).⁸