PS3 (Strong): R158L is non-functional on Kato et al. transactivation assay and demonstrates loss of function across all eligible functional assays (Funk, Giacomelli, Kotler), meeting the VCEP rule for PS3 at Strong strength.¹ PM5 (Strong): At least three different missense variants at codon 158 (R158G, R158H, R158P) carry PS3 assignments per the VCEP Functional-worksheet, meeting the VCEP rule for PM5 at Strong strength (≥2 different pathogenic missense variants at the same residue).² PM1 (Moderate): The variant has 181 somatic occurrences in COSMIC, exceeding the VCEP threshold of ≥10 somatic occurrences for the same amino acid change, meeting PM1 at Moderate strength.³ PP3 (Moderate): Per VCEP PP3-BP4-codes.xlsx, c.473G>T is assigned PP3_moderate (aGVGD Class C65, BayesDel 0.576, REVEL 0.891).⁴ PM2 (Supporting): Variant is extremely rare in gnomAD (v2.1: 1/251,268; v4.1: 1/1,614,128), far below the VCEP PM2_Supporting threshold of <0.003%.⁵ PP5 (Supporting): The ClinGen TP53 VCEP has classified this variant as Pathogenic (ClinVar Variation ID 528248, expert panel reviewed).⁶ BA1, BS1, BS3, BP4 not met: Population frequencies are far below benign thresholds. Functional data demonstrate complete loss of function, contradicting BS3. In silico predictions are decisively pathogenic, contradicting BP4.⁷ PVS1, PS1, PS2, PS4, PS5, PM6, PP1, PP2, PP4, BS2, BS4, BP1, BP2, BP3, BP5, BP6, BP7 not applicable or not assessed due to variant type, VCEP rules, or absence of required evidence.⁸