Is TP53 p.Phe113Cys (c.338T>G) pathogenic?

TP53 p.Phe113Cys (c.338T>G) is classified Pathogenic in TP53 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.9677); No allele count reported in gnomAD v4.1 (AN 1,612,338); Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Phe113Cys (c.338T>G)?

TP53 p.Phe113Cys (c.338T>G) is associated with Li-Fraumeni syndrome, ovarian neoplasm (ClinVar).

How common is TP53 p.Phe113Cys (c.338T>G) in the general population?

TP53 p.Phe113Cys (c.338T>G) is no allele count reported in gnomAD v4.1 (AN 1,612,338) (gnomAD).

How is Li-Fraumeni syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TP53 p.Phe113Cys (c.338T>G)?

AlphaMissense predicts likely pathogenic (score 0.9677) — an in-silico prediction, not a clinical call.

TP53 p.Phe113Cys

c.338T>G · rs1567555667 · VCV634690

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9677 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,338)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Li-Fraumeni syndrome

Computational evidence

Protein change
AlphaMissense	0.9677	likely pathogenic ✓ concordant with ClinVar
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -11.64	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,338). 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.Phe113Cys
Coding: c.338T>G
MANE Select: NM_000546
dbSNP: rs1567555667
Type: single nucleotide variant
Location: chr17:7676031 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 113: a DNA-binding region; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; the 'required for interaction with fbxo42' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Li-Fraumeni syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also 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.Phe113Ile Likely pathogenic ★★★ same residue
TP53 p.Phe113Val Likely pathogenic ★★★ same residue
TP53 p.Phe113Ser Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Phe113Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Phe113_Gly117del Pathogenic ★ same residue
TP53 p.Phe113del Conflicting classifications of pathogenicity ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+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-phe113cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown