PM2_Supporting is met: NM_000546.6:c.293C>G (p.Pro98Arg) is absent from gnomAD v2.1 and v4.1 (0 alleles across all populations), satisfying the VCEP PM2_Supporting threshold of allele frequency <0.00003.¹ PP3_Moderate is met: The VCEP PP3-BP4-codes.xlsx assigns PP3_moderate for c.293C>G. This variant has aGVGD Class C65 and BayesDel score 0.591769 (≥0.16), with no predicted splicing impact (SpliceAI max delta 0.00). REVEL score of 0.955 provides additional in silico support.² PVS1 is not applicable: this is a missense variant; the TP53 VCEP reserves PVS1 for null variants (nonsense, frameshift, canonical splice, initiation codon, exon deletions).³ PS3 and BS3 are not met: the VCEP Functional-worksheet.xlsx assigns 'No evidence' for p.Pro98Arg. Kato class is 'Partially functional' and Giacomelli reports 'noLOF', which does not satisfy VCEP PS3 or BS3 criteria thresholds.⁴ PM1 is not met: codon 98 is not among the VCEP-defined hotspot codons (175, 245, 248, 249, 273, 282), and the residue is not a statistically significant hotspot on cancerhotspots.org. PM5 is not met: no other Pro98 missense variant has a VCEP P/LP classification.⁵ PS1, PS2, PS4, PP1, PP4, BA1, BS1, BS2, BS3, BS4, BP4 are not met based on absence of qualifying evidence from ClinVar, gnomAD, published literature, and VCEP reference data.⁶ PP5, BP1, BP2, BP5, BP6, PM6, PP2, and BP3 are not applicable under the TP53 VCEP v2.4.0 specifications. PS5 is not included in the VCEP criteria set. BP7 is not applicable as this is a missense variant.⁷ Tavtigian point tally: PM2_Supporting (+1) + PP3_Moderate (+2) = 3 points. Per TP53 VCEP v2.4.0 ranges: ≥10 Pathogenic, 6-9 Likely Pathogenic, -1 to 5 Uncertain Significance, -6 to -2 Likely Benign, ≤-7 Benign. Total of 3 points classifies this variant as Uncertain Significance (VUS).⁸