NM_000546.5:c.580delC (p.Ile195SerfsTer52) is a frameshift deletion in exon 6 of TP53, producing a premature termination codon at position 246, upstream of p.Lys351, and is predicted to undergo nonsense-mediated decay. Under the TP53 VCEP PVS1 decision tree (v2.4.0), PVS1 is applied at very strong weight (8 points).¹ This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0. Under the TP53 VCEP PM2 specifications, variants with an allele frequency below 0.00003 qualify for PM2 at supporting level (1 point).² The variant is absent from ClinVar and has not been reported in COSMIC. No variant-specific functional data are available from the TP53 VCEP functional worksheet (which covers missense and in-frame deletions only). No proband phenotype, de novo, segregation, or VAF data are available in the case materials to assess PS2, PS4, PP1, PP4, BS2, or BS4.³ Total weighted points: PVS1 (8) + PM2_Supporting (1) = 9 points. Per the TP53 VCEP Tavtigian Bayesian point-based classification framework (v2.4.0), 6-9 points corresponds to Likely Pathogenic.⁴