Is TP53 p.Val157= (c.471C>A) pathogenic?

TP53 p.Val157= (c.471C>A) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-13). Very rare (popmax 0.000169%, nfe); Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Val157= (c.471C>A)?

TP53 p.Val157= (c.471C>A) is associated with Li-Fraumeni syndrome 1, colorectal cancer, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Val157= (c.471C>A) in the general population?

TP53 p.Val157= (c.471C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

TP53 p.Val157=

c.471C>A · rs1057522496 · VCV386420

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Li-Fraumeni syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.032	GERP -5, phastCons 0.26
Overall
CADD	1.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,048 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,886 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TP53
Protein: p.Val157=
Coding: c.471C>A
MANE Select: NM_000546
dbSNP: rs1057522496
Type: single nucleotide variant
Location: chr17:7675141 (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

Li-Fraumeni syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer hereditary neoplastic syndrome Li-Fraumeni syndrome

Similar variants

TP53 p.Val157Ile Likely benign ★★★ same residue
TP53 p.Val157Phe Pathogenic/Likely pathogenic ★★ 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_Arg158del Likely pathogenic ★ same residue
TP53 p.Val157Gly Likely pathogenic ★ same residue
TP53 p.Val157_Arg158dup Uncertain significance ★ 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-val157 (accessed [today's date]).

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