NM_000546.5:c.684C>G (p.Asp228Glu) is a missense variant in exon 7 of TP53. The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (PM2_Supporting; +1 point).¹ Functional evidence from the TP53 VCEP Functional-worksheet demonstrates the variant retains wild-type-like function: Kato et al. assay shows Functional activity, and all eligible assays (Giacomelli, Kotler, Kawaguchi) report no loss of function (BS3; -4 points).² In silico evidence supports a benign interpretation: BayesDel score is -0.133538 (Class C0), and SpliceAI predicts no splicing impact (max delta 0.00). The VCEP PP3-BP4-codes spreadsheet assigns BP4_moderate (-2 points).³ Codon 228 is not among the VCEP-defined hotspot codons (175, 245, 248, 249, 273, 282), and the variant is not listed in cancerhotspots.org; PM1 is not met. PP3 is not met per VCEP in silico flowchart: BayesDel score does not meet the ≥0.16 threshold and aGVGD class is C0.⁴ PS3 is not met: the functional evidence favors a benign interpretation; the VCEP pre-assigned code is BS3, not PS3.⁵ Total points: PM2_Supporting (+1) + BS3 (-4) + BP4_Moderate (-2) = -5. Per the Tavtigian Bayesian point-based framework (TP53 VCEP v2.4.0), a score of -5 falls in the Likely Benign range (-6 to -2).⁶ This variant has been reported in ClinVar as Uncertain significance by 5 clinical laboratories and as Likely benign by 1 clinical laboratory (ClinVar ID: 926556).⁷ COSMIC reports 6 somatic occurrences (COSV52662428). OncoKB classifies the variant as Likely Oncogenic with likely loss-of-function effect, which is inconsistent with the VCEP functional data showing retained function; the VCEP functional worksheet takes precedence for germline classification.⁸ No de novo, segregation, proband, or case-control data are available; PS2, PS4, PP1, PP4, BS2, and BS4 remain unassessed.