TP53 p.Pro151His
c.452C>A · rs1057520000 · VCV376639
Computational evidence
| Protein change | ||
| AlphaMissense | 0.992 | likely pathogenic · top 8% in TP53 |
|---|---|---|
| REVEL | 0.87 | moderately pathogenic-leaning |
| SaProt | LLR -15.83 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic |
| Overall | ||
| CADD | 24.7 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Cancer therapy — CIViC
| Disease | Therapies | Level | Significance |
|---|---|---|---|
| D | Dominant Negative | ||
| D | Unaltered Function |
Variant & gene context
- Gene
- TP53
- Protein
- p.Pro151His
- Coding
- c.452C>A
- MANE Select
- NM_000546
- dbSNP
- rs1057520000
- Type
- single nucleotide variant
- Location
- chr17:7675160 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.83 · 321 PDB
- Residue 151
- a DNA-binding region; the 'interaction with axin1' region; an α-helix; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; the 'required for interaction with fbxo42' region
Disease context
Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: ovarian neoplasm
For Li-Fraumeni syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (United Kingdom)
Similar variants
- TP53 p.Pro151Ala Pathogenic ★★ same residue
- TP53 p.Pro151Arg Pathogenic/Likely pathogenic ★★ same residue
- TP53 p.Pro151Ser Pathogenic/Likely pathogenic ★★ same residue
- TP53 p.Pro151Thr Pathogenic/Likely pathogenic ★★ same residue
- TP53 p.Pro151= Likely benign ★★ same residue
- TP53 c.375+5G>A Likely pathogenic ★★★ same condition
- TP53 c.919+1G>A Pathogenic ★★★ same condition
- TP53 c.97-1G>A 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/tp53-p-pro151his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown