PVS1 is not applicable. NM_000340.2:c.1094G>A is a missense variant (p.Arg365Gln), not a null variant meeting ClinGen SVI PVS1 criteria.¹ PM2 (Supporting) is met. The variant is present in gnomAD at extremely low frequency — v2.1 AF 2.13e-05 (6/282,168 alleles), v4.1 AF 1.99e-05 (32/1,611,868 alleles), grpmax FAF 1.13e-05 to 8.17e-05 — well below the 0.1% threshold. Absent from gnomAD-Canada. Zero homozygotes observed.² PP3 (Supporting) is met. Multiple computational predictors support a deleterious effect: REVEL score 0.84 (strongly pathogenic range, >0.5), BayesDel no-AF score 0.352 (above deleterious threshold >0.27). SpliceAI predicts no splicing impact (delta 0.0), consistent with a coding missense variant.³ No pathogenic criteria beyond PM2 and PP3 (both supporting) are met. No benign criteria are met. All moderate, strong, and very strong criteria are either not applicable, not assessed, or not met. Per ACMG/AMP 2015 combination rules (PMID:25741868), two supporting pathogenic criteria (PM2_Supporting + PP3_Supporting) are insufficient to reach Likely Pathogenic. The variant is classified as a Variant of Uncertain Significance (VUS).⁴