This variant is absent from gnomAD v2.1 and gnomAD-Canada, and present at extremely low frequency in gnomAD v4.1 (1/1,206,311 alleles, AF 8.29e-07), meeting PM2 at supporting level.¹ Multiple lines of in silico evidence predict no deleterious effect: SpliceAI max delta = 0.02 (no splicing impact) and BayesDel score = 0.226 (below pathogenic threshold), meeting BP4 at supporting benign level.² PVS1 is not applicable as this is a missense variant (p.Arg20Gln), not a predicted null variant.³ No functional data, case-control studies, segregation data, or variant-specific publications were identified. PS3, PS4, and PM1 are not met.⁴ ClinVar reports this variant as Uncertain significance (1 clinical laboratory, criteria provided). No expert panel classification is available.⁵ The available evidence is insufficient to classify this variant as pathogenic or benign. One supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, leaving the variant as a Variant of Uncertain Significance (VUS) under ACMG/AMP 2015 rules.⁶