Is TP53 p.Val272= (c.816G>A) pathogenic?

TP53 p.Val272= (c.816G>A) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-01). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Val272= (c.816G>A)?

TP53 p.Val272= (c.816G>A) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Val272= (c.816G>A) in the general population?

TP53 p.Val272= (c.816G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TP53 p.Val272=

c.816G>A · rs756421198 · VCV1136213

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

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

Conditions

hereditary neoplastic syndrome

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 -4.1	GERP -5.1
Overall
CADD	3.159	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,988 alleles

Overall 6.2e-05% 1/1,614,020 alleles · very rare exomes 1/1,461,808 · genomes 0/152,212 · joint denominator

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.Val272=
Coding: c.816G>A
MANE Select: NM_000546
dbSNP: rs756421198
Type: single nucleotide variant
Location: chr17:7673804 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 272: a DNA-binding region; the 'interaction with axin1' 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 e4f1' region; a β-strand; 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

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

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Val272Met Pathogenic ★★★ same residue
TP53 p.Val272Leu Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Val272Ala Uncertain significance ★★ ⚠ same residue
TP53 p.Val272Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Val272Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Val272fs Pathogenic ★ same residue
TP53 p.Val272_Arg273insLeu 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-val272 (accessed [today's date]).

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