PS3_Strong is met (+4 points): N239S is non-functional in the Kato et al. functional assay and shows loss of function in all three other eligible VCEP assays (Giacomelli, Kotler, Funk), meeting the TP53 VCEP criterion for strong pathogenic functional evidence.¹ PM5_Strong is met (+4 points): At codon 239, three different missense variants (N239D, N239I, N239T) have been classified as pathogenic (PS3) by the TP53 VCEP, satisfying the requirement of ≥2 different pathogenic missense variants at the same residue.² PM2_Supporting is met (+1 point): The variant is extremely rare in population databases (gnomAD v4.1 AF = 6.2e-7), well below the VCEP threshold of <0.00003.³ BP4_Supporting is met (-1 point): Per the VCEP PP3-BP4-codes.xlsx, c.716A>G is assigned BP4. BayesDel score 0.10537 with aGVGD Class C45 and no predicted splicing impact (SpliceAI 0.04).⁴ Tavtigian point total: 4 (PS3) + 4 (PM5) + 1 (PM2) - 1 (BP4) = 8 points. Under the TP53 VCEP v2.4.0 point-based framework, 6-9 points corresponds to Likely Pathogenic.⁵ The variant has been observed in ClinVar with majority classification as Likely Pathogenic (6 clinical laboratories) and Pathogenic (1 laboratory), consistent with this adjudication.⁶ N239S has been reported as a somatic mutation in 56 tumor samples in COSMIC and is classified as Oncogenic (Loss-of-function) by OncoKB, though these somatic data are not directly used for germline criterion points under the VCEP framework.⁷