NM_004304.4:c.4033G>A (p.Gly1345Arg) is absent from gnomAD v2.1 and present at extremely low frequency in gnomAD v4.1 (AF 1.86 × 10⁻⁶, 3/1,613,830 alleles), meeting PM2 at supporting strength.¹ The variant is a missense substitution not located in a statistically significant mutational hotspot; PM1 is not met. In silico predictions are conflicting: REVEL score 0.786 supports a deleterious effect, but BayesDel score 0.144 is in the benign range and SpliceAI max delta 0.20 is borderline. PP3 is not met, and BP4 is not met.² This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratory, SCV002134937); no reputable source classifies it as pathogenic or benign. PP5 and BP6 are not met.³ No variant-specific functional studies (PS3/BS3), segregation data (PP1/BS4), de novo observations (PS2/PM6), or case-control data (PS4) were identified. PVS1 is not applicable as this is a missense variant outside canonical null-variant categories.⁴ With only PM2_Supporting met, the variant does not reach a Likely Pathogenic threshold (requiring at least 2 Supporting criteria or 1 Moderate + 1 Supporting under generic ACMG/AMP rules) nor a Likely Benign threshold. The variant remains a Variant of Uncertain Significance.⁵