NM_000546.5:c.214_215delinsTG (p.Pro72Cys) is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2_Supporting per TP53 VCEP criteria (allele frequency <0.003%).¹ PVS1 is not applicable as the variant is an in-frame delins resulting in a single amino acid substitution (p.Pro72Cys), not a null variant covered by the VCEP PVS1 flowchart.² No functional data (PS3/BS3) is available for this variant; p.Pro72Cys is not listed in the VCEP Functional-worksheet and no variant-specific functional studies were identified in the reviewed literature.³ No pathogenic or likely pathogenic variant has been established at codon 72 (Pro72), which precludes application of PS1 and PM5. All single-nucleotide missense variants at this residue receive BP4_moderate per the VCEP.⁴ In silico scores (REVEL, BayesDel) are not computable for delins variants, precluding PP3/BP4 assessment.⁵ Codon 72 is not a recognized TP53 hotspot; the variant lies outside VCEP-designated hotspot codons 175, 245, 248, 249, 273, and 282, and is not listed in cancerhotspots.org.⁶ No proband clinical data, de novo observations, segregation data, or elderly cancer-free carrier data are available for this variant, precluding PS2, PS4, PP1, PP4, BS2, and BS4. This variant has been reported in ClinVar as Uncertain Significance, with 7 clinical laboratories reporting Uncertain Significance, 1 reporting Likely Benign, and the ClinGen TP53 VCEP Expert Panel classifying as Uncertain Significance (ClinVar ID: 182953).⁷ Applying the TP53 VCEP Tavtigian point-based classification system: only PM2_Supporting (1 point) is met, yielding a total of 1 point, which falls within the Uncertain Significance range (-1 to 5 points).⁸