TP73 p.His418=
c.1254C>T · rs139554277 · VCV734875
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.752%, afr)
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 -20 | GERP -4.5 |
| Overall | ||
| CADD | 0.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.752%
African / African-American · 564/74,976 alleles
Filtering AF
0.701%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.68%
Overall
0.057%
916/1,607,756 alleles · rare
exomes 548/1,455,414 · genomes 368/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.752% | 133 |
| South Asian | 0.129% | 775 |
| Admixed American | 0.103% | 975 |
| Remaining individualsnot grpmax-eligible | 0.0851% | 1,175 |
| Middle Eastern | 0.0166% | 6,032 |
| European (non-Finnish) | 0.01% | 9,980 |
| Finnishnot grpmax-eligible | 0.0032% | 31,205 |
| East Asian | 0.00224% | 44,730 |
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
- TP73
- Protein
- p.His418=
- Coding
- c.1254C>T
- MANE Select
- NM_005427
- dbSNP
- rs139554277
- Type
- single nucleotide variant
- Location
- chr1:3730057 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.25 · 28 PDB
- Residue 418
- a UniProt-annotated variant site (in cild47)
Similar variants
- TP73 p.His418Gln Uncertain significance ★ ⚠ same residue
- TP73 p.Arg538Cys Uncertain significance ★★ ⚠ same type
- TP73 p.Gly451Arg Uncertain significance ★★ ⚠ same type
- TP73 c.65+9G>A Benign/Likely benign ★★ same type
- TP73 p.Ala325Thr Benign ★★ same type
- TP73 p.Gln391= Benign ★★ same type
- TP73 p.Ser563= Benign ★★ same type
- TP73 p.Thr136= Benign/Likely benign ★★ 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/tp73-p-his418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown