TP53 p.Ser392fs
c.1174_1175del · VCV3649133
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Li-Fraumeni syndrome
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 | escapes | premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -4.6, phastCons 0.001 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TP53
- Protein
- p.Ser392fs
- Coding
- c.1174_1175del
- MANE Select
- NM_000546
- Type
- Deletion
- Location
- chr17:7669616 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.83 · 321 PDB
- Residue 392
- a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with carm1' region; the 'disordered' region; the 'interaction with morn3' region; a modified residue (phosphoserine; by ck2, cdk2 and nuak1)
Disease context
Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Li-Fraumeni syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (United Kingdom)
Similar variants
- TP53 p.Ser392Pro Uncertain significance ★ ⚠ same residue
- TP53 c.993+1del Likely pathogenic ★★★ same condition
- TP53 p.Ala161_Tyr163delinsAsp Likely pathogenic ★★★ same condition
- TP53 p.Arg213fs Pathogenic ★★★ same condition
- TP53 p.Leu252_Ile254del Pathogenic ★★★ same condition
- TP53 p.Lys382fs Likely pathogenic ★★★ same condition
- TP53 p.Lys373fs Uncertain significance ★★★ same condition
- TP53 c.*772del Benign ★★★ 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-ser392fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown