c.413C>A (p.Ala138Asp) in TP53 is a missense variant in exon 5. It is absent from gnomAD v2.1 and v4.1 (PM2_Supporting).

In silico predictions are consistent with a deleterious effect: aGVGD Class C65, BayesDel 0.540498, REVEL 0.901, and SpliceAI predicts no splicing impact (max delta 0.01). The TP53 VCEP assigns PP3_moderate.

Functional data from the TP53 VCEP Functional-worksheet (Supplementary Table S3) assign 'No evidence' to p.Ala138Asp: Kato shows partially functional, Funk shows LOF, but Giacomelli and Kotler show noLOF. Neither PS3 nor BS3 criteria are met.

The variant is not located in a VCEP-specified PM1 hotspot codon (175, 245, 248, 249, 273, 282), and the exact variant is not listed in cancerhotspots.org (PM1 not met).

This variant has been reported in ClinVar as Uncertain Significance by the ClinGen TP53 Variant Curation Expert Panel (ClinVar ID: 528270) and has been observed 3 times in somatic cancers (COSMIC COSV53502932).

PVS1, PS5, PM6, PP2, PP5, BP1, BP2, BP5, BP6, and BP7 are not applicable per the TP53 VCEP v2.4.0 specifications or by variant type. PS1, PS2, PS4, PM5, PP1, PP4, BS2, BS4, and BS5 remain not assessed due to insufficient clinical data.