TP73 p.Ser563=
c.1689T>C · rs116174056 · VCV775492
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele
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 0.93 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 11.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.78%
African / African-American · 5,089/75,028 alleles
Filtering AF
6.63%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.56%
Overall
0.358%
5,767/1,612,078 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.78% | 15 |
| Admixed American | 0.465% | 215 |
| Remaining individualsnot grpmax-eligible | 0.421% | 238 |
| Middle Eastern | 0.363% | 276 |
| South Asian | 0.0231% | 4,334 |
| European (non-Finnish) | 0.00788% | 12,685 |
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.Ser563=
- Coding
- c.1689T>C
- MANE Select
- NM_005427
- dbSNP
- rs116174056
- Type
- single nucleotide variant
- Location
- chr1:3732857 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.25 · 28 PDB
- Residue 563
- a UniProt-annotated variant site (in cild47)
Similar variants
- 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.His418= Benign/Likely benign ★★ same type
- TP73 p.Thr136= Benign/Likely benign ★★ same type
- TP73 p.Thr247= 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-ser563 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown