TP73 p.His349=
c.1047T>C · rs12048341 · VCV3055835
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 17.7%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
TP73-related disorder
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 -9.7 | GERP -3.2 |
| Overall | ||
| CADD | 0.097 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17.7%
African / African-American · 13,307/74,986 alleles
Filtering AF
17.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 17.4%
Overall
4.89%
78,853/1,611,698 alleles · common
exomes 65,850/1,459,488 · genomes 13,003/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 17.7% | 6 |
| East Asian | 17.4% | 6 |
| Amishnot grpmax-eligible | 9.21% | 11 |
| Remaining individualsnot grpmax-eligible | 6.19% | 16 |
| Middle Eastern | 5.89% | 17 |
| Finnishnot grpmax-eligible | 5.55% | 18 |
| Ashkenazi Jewishnot grpmax-eligible | 5.42% | 18 |
| European (non-Finnish) | 3.75% | 27 |
| Admixed American | 3.19% | 31 |
| South Asian | 2.49% | 40 |
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.His349=
- Coding
- c.1047T>C
- MANE Select
- NM_005427
- dbSNP
- rs12048341
- Type
- single nucleotide variant
- Location
- chr1:3728190 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.25 · 28 PDB
- Residue 349
- a UniProt-annotated variant site (in cild47); the 'oligomerization' region; the 'interaction with hipk2' region
Disease context
TP73-related disorder
Similar variants
- TP73 p.Ala336= Benign same condition
- TP73 p.Ile626Val Likely benign same condition
- TP73 p.Val586Met Likely benign ⚠ same condition
- 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
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-his349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown