TP53 p.Arg65Ter
c.193A>T · rs1555526721 · VCV634670
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ovarian neoplasm
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 11 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.022 | GERP -2.5 |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TP53
- Protein
- p.Arg65Ter
- Coding
- c.193A>T
- MANE Select
- NM_000546
- dbSNP
- rs1555526721
- Type
- single nucleotide variant
- Location
- chr17:7676176 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.83 · 321 PDB
- Residue 65
- a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region
Similar variants
- TP53 p.Arg65= Benign/Likely benign ★★ same residue
- TP53 p.Arg65Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- TP53 p.Arg65Thr Uncertain significance ★ ⚠ same residue
- TP53 c.375+5G>A Likely pathogenic ★★★ same condition
- TP53 p.Arg110Leu Pathogenic ★★★ ⚠ same condition
- TP53 p.Arg175Gly Pathogenic ★★★ same condition
- TP53 p.Arg175His Pathogenic ★★★ same condition
- TP53 p.Arg248Gln 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-arg65ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown