TP53 p.Arg213fs
c.636del · rs864309495 · VCV218342
ClinGen expert panel — TP53 VCEP
Pathogenic for Li-Fraumeni syndrome 1. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting PS4_Supporting
Curation rationale (ClinGen, verbatim)
The p.R213fs variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in 2 probands meeting Chompret criteria (PS4_Supporting; PMID: 11370630, NIH). In summary, TP53 c.636del (p.R213fs) meets criteria to be classified as pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PVS1, PM2_Supporting, PS4_Supporting.
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. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 11 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6.3 | GERP 0.088, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Arg213fs
- Coding
- c.636del
- MANE Select
- NM_000546
- dbSNP
- rs864309495
- Type
- Deletion
- Location
- chr17:7674895 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.83 · 321 PDB
- Residue 213
- a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; the 'interaction with hipk1' 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 'required for interaction with znf385a' region; the 'required for interaction with fbxo42' region
Similar variants
- TP53 p.Arg213_Tyr220del Likely pathogenic ★ same residue
- TP53 p.Arg213Gln Pathogenic/Likely pathogenic ★★ same residue
- TP53 p.Arg213Pro Pathogenic/Likely pathogenic ★★ same residue
- TP53 p.Arg213Ter Pathogenic ★★ same residue
- TP53 p.Arg213Trp Pathogenic/Likely pathogenic ★★ same residue
- TP53 p.Arg213Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- TP53 p.Arg213Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- TP53 p.Arg213= Benign ★ 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-arg213fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown