Functional studies demonstrate that p.Tyr234Asn is non-functional in the Kato et al. transactivation assay with loss of function across all other eligible assays (Giacomelli, Kotler, Funk), meeting PS3 at strong strength per the TP53 VCEP v2.4.0 Functional-worksheet.
This variant is absent from gnomAD v2.1 and v4.1 population databases (allele count = 0), meeting PM2_Supporting per the TP53 VCEP threshold of allele frequency <0.003%.
gnomad_v2 ↗ gnomad_v4 ↗Computational evidence supports a deleterious effect: aGVGD Class C35, BayesDel score 0.489, REVEL score 0.941, with no predicted splicing impact (SpliceAI max delta 0.00). The TP53 VCEP PP3-BP4-codes spreadsheet assigns PP3 at supporting level.
spliceai ↗This variant has been reported in ClinVar as Pathogenic by two clinical laboratories and Likely pathogenic by one laboratory (ClinVar Variation ID 376692), and has been observed in somatic cancers (COSMIC, n=35).
clinvar ↗Applying the TP53 VCEP v2.4.0 Tavtigian point system: PS3_Strong (+5) + PM2_Supporting (+1) + PP3_Supporting (+0.5) = 6.5 total points, which falls within the Likely Pathogenic range (6-9 points).
cspec ↗
