NM_000546.6:c.370T>C (p.Cys124Arg) is a missense variant in TP53 exon 4. This variant is absent from gnomAD v2.1 and v4.1 (PM2_Supporting).¹ Functional studies demonstrate that p.Cys124Arg is non-functional in the Kato transcriptional assay and shows loss of function in both the Giacomelli and Kotler assays, meeting the TP53 VCEP criteria for PS3 (Strong).² In silico prediction tools support a deleterious effect: aGVGD Class C65, BayesDel score 0.25469, and REVEL score 0.883. The TP53 VCEP PP3-BP4-codes.xlsx assigns PP3_moderate.³ SpliceAI predicts no significant splicing impact (max delta score 0.02), consistent with a missense effect rather than a splicing alteration.⁴ This variant has been reported in ClinVar as Likely pathogenic by a single clinical laboratory (SCV006277400).⁵ The variant has been observed in somatic cancers (COSMIC COSV52752618, n=8). Applying the TP53 VCEP v2.4.0 Tavtigian point-based framework: PS3 (Strong) = +4, PM2_Supporting = +1, PP3_moderate = +2. Total points = +7 (range 6-9), consistent with Likely Pathogenic.⁶ No benign criteria are met. No evidence for BA1, BS1, BS2, BS3, BS4, or BP4 was identified.