NM_000546.5:c.509C>T (p.Thr170Met) is a missense variant in exon 5 of TP53. This variant is present at very low frequency in gnomAD v4.1 (AF=1.55e-05, 25/1,614,086 alleles, 0 homozygotes), meeting PM2_Supporting per the TP53 VCEP specifications (total AF < 0.003%; no non-founder subpopulation with multiple alleles exceeds 0.004%).¹ Functional assay data from the TP53 VCEP Functional-worksheet.xlsx (Supplementary Table S3) demonstrates that p.Thr170Met is partially functional in the Kato et al. yeast transactivation assay and shows no loss of function across all available eligible assays (Funk, Giacomelli, Kotler), meeting BS3_Supporting per the VCEP functional rules.² In silico predictions were evaluated per the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), which assigns 'No evidence' for c.509C>T — neither PP3 nor BP4 is met. The variant has aGVGD Class C15 and BayesDel score 0.321305.³ The variant has been reported in ClinVar with an expert panel classification of Likely Benign by the ClinGen TP53 Variant Curation Expert Panel (ClinVar ID: 184014). It has been observed in COSMIC as a somatic variant (n=14) but does not lie in a statistically significant cancer hotspot.⁴ PVS1, PS1, PS2, PS4, PS5, PM1, PM5, PM6, PP1, PP2, PP4, PP5, BA1, BS1, BS2, BS4, BP1, BP2, BP4, BP5, BP6, and BP7 are either not met, not assessed due to lack of evidence, or not applicable per the TP53 VCEP specifications.⁵ Tavtigian point total: PM2_Supporting (+1) + BS3_Supporting (−1) = 0 points, corresponding to a final classification of Uncertain Significance (VUS) per the TP53 VCEP v2.4.0 point-based system (VUS range: −1 to 5).⁶