NM_000546.6:c.431_436del (p.Gln144_Trp146delinsArg) is a 6-bp in-frame deletion in exon 5 of TP53, removing two amino acids (Q144 and W146) in the DNA-binding core domain L2 loop region and inserting arginine. This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, consistent with PM2_Supporting (allele frequency < 0.003%).¹ The variant has not been reported in ClinVar and has not been observed in COSMIC.² SpliceAI predicts no splicing impact (max delta score = 0.00).³ The variant is not covered by the VCEP PVS1 framework (in-frame deletion, not a null variant), nor by VCEP PP3/BP4 in silico rules (multi-amino-acid deletion, not a missense or single-AA deletion).⁴ No variant-specific functional assay data from eligible studies (Kato, Kotler, Giacomelli, Funk, Kawaguchi) are available; the VCEP Functional worksheet does not contain this variant. OncoKB infers a Likely Loss-of-function but this is a somatic curation and not a direct germline functional assay.⁵ No proband data, segregation data, de novo observations, or cancer-phenotype data were available for this variant. Only one criterion met: PM2_Supporting. All other applicable criteria are either not met, not assessed due to absent data, or not applicable per VCEP specifications.