NM_000535.6:c.1321G>T (p.Glu441Ter) is a nonsense variant in PMS2 exon 11 introducing a premature termination codon at position 441, which is well before the VCEP-defined PVS1 boundary at codon 798.¹ This variant meets PVS1 at Very Strong strength under the InSiGHT PMS2 VCEP v2.0 criteria for nonsense variants introducing a PTC ≤ codon 798.² The variant is absent from gnomAD v2.1 and v4.1 population databases (0 alleles), meeting PM2 at Supporting strength under VCEP criteria (<0.00002 allele frequency threshold).³ No variant-specific functional data, de novo observations, cosegregation data, or tumor phenotype data were identified in the case materials or reviewed literature. SpliceAI predicts no significant splice impact (max delta 0.03), confirming that the primary molecular consequence is protein truncation rather than aberrant splicing.⁴ Under the InSiGHT PMS2 VCEP v2.0 combination rules, 1 Very Strong criterion (PVS1) plus 1 Supporting criterion (PM2) is sufficient for a Pathogenic classification (Rule 1 or Rule 4).⁵