NM_000546.5:c.214C>T (p.Pro72Ser) is a missense variant in exon 4 of TP53 at codon 72, a known common polymorphic site (rs1042522). The variant is present at very low frequency in gnomAD v2.1 (4/250,672 alleles; AF=0.00160%) and v4.1 (11/1,613,668 alleles; AF=0.00068%), meeting the TP53 VCEP PM2_Supporting threshold of <0.003% total allele frequency with subpopulation AF <0.004%.¹ The variant is assigned BP4_moderate by the TP53 VCEP bioinformatic codes (Supplementary Table S2), with a BayesDel score of -0.202922 and no predicted splicing impact (SpliceAI max delta = 0.00).² The variant has been reported in ClinVar as Likely benign (Ambry Genetics, 1 submission) and Uncertain significance (Labcorp/Invitae, 1 submission). No expert panel review is available. (ClinVar VariationID: 485023)³ The variant has been observed in somatic cancers (COSMIC, COSV52665238, n=6), but lies outside the TP53 VCEP-defined mutational hotspots (codons 175, 245, 248, 249, 273, 282). No functional data from VCEP-eligible assays are available for p.Pro72Ser; the variant is absent from the VCEP Functional-worksheet (Supplementary Table S3). Under the Tavtigian point-based system (TP53 VCEP v2.4.0), the evidence tally is PM2_Supporting (+1) + BP4_Moderate (-2) = -1 point, consistent with a classification of Uncertain Significance. The VCEP CAVEAT allowing reclassification of -1 points to Likely Benign (requiring ≥2 benign codes and PM2_Supporting as the only pathogenic code) is not met, as only one benign code (BP4_Moderate) is applied.