Is TP53 p.Glu286Val (c.857A>T) pathogenic?

TP53 p.Glu286Val (c.857A>T) is classified Pathogenic in TP53 (ClinVar, Expert panel, 3 submitters; last evaluated 2026-08-06). AlphaMissense: likely pathogenic (0.9153); Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Glu286Val (c.857A>T)?

TP53 p.Glu286Val (c.857A>T) is associated with Li-Fraumeni syndrome, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Glu286Val (c.857A>T) in the general population?

TP53 p.Glu286Val (c.857A>T) is absent from gnomAD v4.1 (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.Glu286Val (c.857A>T)?

AlphaMissense predicts likely pathogenic (score 0.9153) — an in-silico prediction, not a clinical call.

TP53 p.Glu286Val

c.857A>T · rs1057519985 · VCV376592

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9153 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Li-Fraumeni syndrome

Computational evidence

Protein change
AlphaMissense	0.9153	likely pathogenic ✓ concordant with ClinVar
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -14.15	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 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	28.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP53
Protein: p.Glu286Val
Coding: c.857A>T
MANE Select: NM_000546
dbSNP: rs1057519985
Type: single nucleotide variant
Location: chr17:7673763 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 286: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with e4f1' region; a UniProt-annotated variant site (in 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 a sporadic cancer; somatic mutation; requires 2 nucleotide substitutions); the 'disordered' region; an α-helix; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' 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: hereditary neoplastic syndrome

For Li-Fraumeni syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (United Kingdom)

Similar variants

TP53 p.Glu286Lys Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Glu286Ter Pathogenic ★ same residue
TP53 p.Glu286Asp Uncertain significance ★ ⚠ same residue
TP53 p.Glu286Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Glu286Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Glu286= Likely benign ★ same residue
TP53 p.Glu286fs Pathogenic ★ same residue
TP53 p.Glu286Ala Likely pathogenic ★ 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-glu286val (accessed [today's date]).

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