PM2 at supporting: NM_005247.2:c.121G>T (p.Gly41Trp) is present at extremely low frequency in gnomAD v4.1 (AF=0.00195%, 29/1,489,482 alleles, 0 homozygotes, grpmax FAF=1.52e-05) and is absent from gnomAD v2.1 and gnomAD-Canada.¹ BP4 at supporting_benign: Multiple in silico algorithms predict a benign effect (REVEL 0.432, BayesDel -0.07, SpliceAI max delta 0.00) with no evidence of splicing impact or hotspot localization.² PVS1 is not applicable as this is a missense variant, not a null variant (nonsense, frameshift, or canonical splice site).³ No pathogenic or likely pathogenic classification from ClinVar expert panels is available (variant is absent from ClinVar); PS5 and PP5 are not met. PS1 and PM5 are not met as no pathogenic comparator variants exist at residue Gly41.⁴ No variant-specific functional studies, case-control data, segregation data, de novo reports, or phenotype data are available; PS3, PS4, PS2, PM6, PP1, PP4, BS2, BS4, BP2, and BP5 remain not assessed.⁵ BA1 and BS1 are not met as the population frequency (AF=0.00195%) is well below both the 1% and 0.3% thresholds respectively.⁶ Final classification: Variant of Uncertain Significance (VUS). One supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, which are offsetting. No other criteria are met. Per generic ACMG/AMP 2015 combination rules, this does not reach the threshold for Likely Pathogenic, Likely Benign, Pathogenic, or Benign.⁷