Is TP53 p.Val143= (c.429G>A) pathogenic?

TP53 p.Val143= (c.429G>A) is classified Likely benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Val143= (c.429G>A)?

TP53 p.Val143= (c.429G>A) is associated with Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Val143= (c.429G>A) in the general population?

TP53 p.Val143= (c.429G>A) 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.

TP53 p.Val143=

c.429G>A · rs2151033080 · VCV2742385

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Li-Fraumeni 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 0.47	GERP -4.9, phastCons 0.78
Overall
CADD	7.218	PHRED · no single calibrated threshold — expert panels disagree

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.Val143=
Coding: c.429G>A
MANE Select: NM_000546
dbSNP: rs2151033080
Type: single nucleotide variant
Location: chr17:7675183 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 143: 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; strong dna binding ability at 32.5 degrees celsius; strong reduction of transcriptional activity at 37.5 degrees celsius; severely represses interaction with znf385a); 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Li-Fraumeni syndrome (Orphanet):

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

Similar variants

TP53 p.Val143Ala Pathogenic ★★★ same residue
TP53 p.Val143Gly Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Val143Met Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Val143Leu Uncertain significance ★★ ⚠ same residue
TP53 p.Val143fs Pathogenic ★ same residue
TP53 p.Val143Glu Uncertain significance ⚠ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+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-val143 (accessed [today's date]).

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