PS3 (Strong): R175H is non-functional in the Kato et al. systematic functional assay and demonstrates loss of function in all three other eligible VCEP assays (Giacomelli, Kotler, Kawaguchi). This meets the TP53 VCEP v2.4.0 PS3 rule: non-functional on Kato data AND LOF by the majority of other eligible assays.¹ PM1 (Moderate): The variant is located at codon 175, which is explicitly listed in the TP53 VCEP PM1 criteria as a codon where PM1 (Moderate) applies. COSMIC reports 2,560 somatic occurrences at this residue.² PM2 (Supporting): The variant is extremely rare in population databases. gnomAD v4.1 reports an allele frequency of 4.34e-06 (7/1,614,062 alleles), well below the VCEP PM2_Supporting threshold of <0.003%. The highest subpopulation frequency (European non-Finnish) is 5.93e-06, below the <0.004% subpopulation threshold.³ PP3 (Supporting): The VCEP PP3-BP4-codes.xlsx assigns PP3 to c.524G>A. The variant has aGVGD Class C25 and BayesDel score 0.54619 (≥0.16), meeting the VCEP PP3_Supporting rule. SpliceAI predicts no splicing impact (max delta = 0.01).⁴ PS4, PM5, PP1, and PS2 were not assessed due to absent or incomplete proband-level data in the evidence package; the VCEP expert panel's Pathogenic classification on ClinVar suggests these criteria may contribute additional points in the full VCEP curation. The expert panel classification in ClinVar as Pathogenic (ClinVar ID 12374) is noted but the VCEP does not permit PP5 for independent criterion application.⁵ Based on assessable evidence, four criteria are met: PS3 (Strong, +4 points), PM1 (Moderate, +2 points), PM2 (Supporting, +1 point), PP3 (Supporting, +1 point). Total = 8 points. Under the Tavtigian point-based framework adopted by the TP53 VCEP v2.4.0, 8 points falls in the 6-9 range → Likely Pathogenic. The ClinGen TP53 VCEP expert panel has independently classified this variant as Pathogenic on ClinVar, which likely incorporates additional evidence (PS4, PM5, PP1) beyond what is available in the current evidence package.⁶