TP53 p.Pro72Cys
c.214_215delinsTG · rs730882014 · VCV182953
ClinGen expert panel — TP53 VCEP
Uncertain Significance for Li-Fraumeni syndrome. Applied ACMG criteria (verbatim):
PM2_Supporting
Curation rationale (ClinGen, verbatim)
The NM_000546.6: c.214_215delinsTG variant in TP53 is a deletion/insertion variant predicted to cause substitution of proline by cysteine at amino acid 72 (p.Pro72Cys). Although this variant has been observed in germline cases, to our knowledge, this variant has not been reported in individuals meeting classical LFS or Chompret criteria (PS4 not met; Internal lab contributors). This variant has been observed in 4-7 heterozygous unrelated females from the same data source with no personal history of cancer prior to age 60 years and no personal history of sarcoma at any age (BS2_Moderate; Internal lab contributors). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as variant of uncertain clinical significance for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: BS2_Moderate, PM2_Supporting. (Bayesian Points: -1; VCEP specifications version 2.2; 2/6/2025).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP 1.1, phastCons 0.015 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic |
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- TP53
- Protein
- p.Pro72Cys
- Coding
- c.214_215delinsTG
- MANE Select
- NM_000546
- dbSNP
- rs730882014
- Type
- Indel
- Location
- chr17:7676154 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.83 · 321 PDB
- Residue 72
- a UniProt-annotated variant site (in sporadic cancers; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region; the 'interaction with wwox' region
Disease context
Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hereditary neoplastic syndrome
For Li-Fraumeni syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (United Kingdom)
Similar variants
- TP53 p.Pro72Ser Uncertain significance ★★ same residue
- TP53 p.Pro72_Val73delinsArgMet Conflicting classifications of pathogenicity ★ same residue
- TP53 p.Pro72Ala Likely benign ★★★ same residue
- TP53 p.Pro72Arg Benign ★★★ same residue
- TP53 p.Pro72His Benign ★★★ ⚠ same residue
- TP53 p.Pro72fs Pathogenic ★ same residue
- TP53 p.Pro72Gly Uncertain significance ★ same residue
- TP53 p.Pro72Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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-pro72cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown