Is TP53 p.Val31Ile (c.91G>A) pathogenic?

TP53 p.Val31Ile (c.91G>A) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 20 submitters; last evaluated 2026-04-23). AlphaMissense: likely benign (0.0694); Rare (popmax 0.528%, eas); Associated with Breast and/or ovarian cancer.

What condition is associated with TP53 p.Val31Ile (c.91G>A)?

TP53 p.Val31Ile (c.91G>A) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Val31Ile (c.91G>A) in the general population?

TP53 p.Val31Ile (c.91G>A) is rare (popmax 0.528%, eas) (gnomAD).

What do computational predictors say about TP53 p.Val31Ile (c.91G>A)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

TP53 p.Val31Ile

c.91G>A · rs201753350 · VCV127827

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 20 submitters

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.528%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.569	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.98	GERP -3.5
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	11.32	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 0.528% East Asian · 237/44,856 alleles

Filtering AF 0.473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.452%

Overall 0.0156% 252/1,613,564 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.528%	189
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.000593%	168,556

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.Val31Ile
Coding: c.91G>A
MANE Select: NM_000546
dbSNP: rs201753350
Type: single nucleotide variant
Location: chr17:7676387 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 31: an α-helix; the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'transcription activation (acidic)' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation)

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

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome Li-Fraumeni syndrome

Similar variants

TP53 p.Val31Phe Uncertain significance ★★ ⚠ same residue
TP53 p.Val31= Likely benign ★ same residue
TP53 p.Val31fs Pathogenic ★ 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
TP53 p.Ala138Pro Likely pathogenic ★★★ same condition
TP53 p.Ala138Val 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-val31ile (accessed [today's date]).

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