Is TP53 p.Val157Phe (c.469G>T) pathogenic?

TP53 p.Val157Phe (c.469G>T) is classified Pathogenic/Likely pathogenic in TP53 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.9349); Absent from gnomAD v4.1; Associated with squamous cell carcinoma.

What condition is associated with TP53 p.Val157Phe (c.469G>T)?

TP53 p.Val157Phe (c.469G>T) is associated with squamous cell carcinoma, hepatocellular carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Val157Phe (c.469G>T) in the general population?

TP53 p.Val157Phe (c.469G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Val157Phe (c.469G>T)?

AlphaMissense predicts likely pathogenic (score 0.9349) — an in-silico prediction, not a clinical call.

TP53 p.Val157Phe

c.469G>T · rs121912654 · VCV12353

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely pathogenic

0.9349 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,132)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

squamous cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.9349	likely pathogenic ✓ concordant with ClinVar
REVEL	0.708	pathogenic-leaning
SaProt	LLR -10.45	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 1.8	GERP -0.67, phastCons 0.98
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	18.28	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 1,614,132). 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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Cancer	MDM2 Inhibitor AMGMDS3	D	Resistance

Variant & gene context

Gene: TP53
Protein: p.Val157Phe
Coding: c.469G>T
MANE Select: NM_000546
dbSNP: rs121912654
Type: single nucleotide variant
Location: chr17:7675143 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 157: a DNA-binding region; the 'interaction with axin1' region; a β-strand; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; 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

squamous cell carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hepatocellular carcinoma hereditary neoplastic syndrome Li-Fraumeni syndrome ovarian neoplasm

Similar variants

TP53 p.Val157Ile Likely benign ★★★ same residue
TP53 p.Val157= Conflicting classifications of pathogenicity ★ same residue
TP53 p.Val157Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Val157Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Val157Leu Uncertain significance ★ ⚠ same residue
TP53 p.Val157_Arg158dup Uncertain significance ★ same residue
TP53 p.Val157del Uncertain significance ★ same residue
TP53 c.375+5G>A Likely 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-val157phe (accessed [today's date]).

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