NM_001128849.1:c.1333C>T (p.Gln445Ter) is a nonsense variant in exon 8 of SMARCA4, a gene with an established loss-of-function disease mechanism for rhabdoid tumor predisposition syndrome type 2 and Coffin-Siris syndrome, satisfying PVS1 at very strong strength under the ClinGen SVI framework (PMC6185798).¹ This variant is absent from all queried population databases including gnomAD v2.1, v4.1, and gnomAD-Canada, satisfying PM2 at moderate strength.² The variant is absent from ClinVar and has not been reported in any curated clinical database, consistent with a rare variant of uncertain prevalence in affected populations.³ No variant-specific functional studies, de novo observations, case-control data, or cosegregation evidence were identified for this variant in the available literature.⁴ Applying generic ACMG/AMP 2015 combination rules, the evidence totals 10 points (PVS1 very_strong = 8 points; PM2 moderate = 2 points), meeting the threshold for a Pathogenic classification (>=10 points).⁵