Is TP53 p.Val197Ala (c.590T>C) pathogenic?

TP53 p.Val197Ala (c.590T>C) is classified Uncertain significance in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely pathogenic (0.7733); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Val197Ala (c.590T>C)?

TP53 p.Val197Ala (c.590T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Val197Ala (c.590T>C) in the general population?

TP53 p.Val197Ala (c.590T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TP53 p.Val197Ala (c.590T>C)?

AlphaMissense predicts likely pathogenic (score 0.7733) — an in-silico prediction, not a clinical call.

TP53 p.Val197Ala

c.590T>C · VCV3460294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7733	likely pathogenic
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.84e-05% 1/1,461,894 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.Val197Ala
Coding: c.590T>C
MANE Select: NM_000546
Type: single nucleotide variant
Location: chr17:7674941 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 197: a DNA-binding region; the 'interaction with axin1' region; a β-strand; the 'interaction with ccar2' region; a UniProt-annotated variant site (in a familial cancer not matching lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 p.Val197Met Likely pathogenic ★★★ same residue
TP53 p.Val197Leu Uncertain significance ★★ ⚠ same residue
TP53 p.Val197Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Val197Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Val197= Likely benign ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ same condition
TP53 c.97-1G>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-val197ala (accessed [today's date]).

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