TP63 p.Ser129=
c.387G>A · rs151335217 · VCV901000
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.036%, afr)
Conditions
2
ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -5.3 |
| Overall | ||
| CADD | 9.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.036%
African / African-American · 27/74,898 alleles
Filtering AF
0.0254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0219%
Overall
0.00273%
44/1,614,036 alleles · ultra-rare
exomes 30/1,461,892 · genomes 14/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.036% | 2,774 |
| South Asian | 0.0143% | 7,007 |
| East Asian | 0.00223% | 44,888 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.000169% | 590,023 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- TP63
- Protein
- p.Ser129=
- Coding
- c.387G>A
- MANE Select
- NM_003722
- dbSNP
- rs151335217
- Type
- single nucleotide variant
- Location
- chr3:189808334 (GRCh38)
- Gene constraint
- LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.70 · 26 PDB
- Residue 129
- a UniProt-annotated variant site (in); the 'disordered' region
Similar variants
- TP63 p.Arg243Gln Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg243Trp Pathogenic ★★ same condition
- TP63 p.Arg266Gln Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg318Cys Pathogenic ★★ same condition
- TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg319Cys Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg343Gln Pathogenic/Likely pathogenic ★★ same condition
- TP63 p.Arg343Trp Pathogenic ★★ same condition
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-ser129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown