TP63 p.Met1Arg
c.2T>G · VCV4075221
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
start-loss
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ectodermal dysplasia syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | start-loss | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| REVEL | 0.704 | pathogenic-leaning |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 19.8 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TP63
- Protein
- p.Met1Arg
- Coding
- c.2T>G
- MANE Select
- NM_003722 · reported on NM_001114980
- Type
- single nucleotide variant
- Location
- chr3:189789802 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 1
- the 'transcription activation' region
Similar variants
- TP63 p.Met1Ile Likely pathogenic ★ same residue
- TP63 p.Met1Thr Uncertain significance ★ same residue
- TP63 p.Met1Val Uncertain significance ★ same residue
- TP63 p.Gly173Asp Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Ala354Glu Likely pathogenic ★★ same type
- TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same type
- TP63 p.Arg243Trp Pathogenic ★★ same type
- TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tp63-p-met1arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown