Is TP53 p.Pro142= (c.426T>C) pathogenic?

TP53 p.Pro142= (c.426T>C) is classified Likely benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Absent from gnomAD v4.1; Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Pro142= (c.426T>C)?

TP53 p.Pro142= (c.426T>C) is associated with Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Pro142= (c.426T>C) in the general population?

TP53 p.Pro142= (c.426T>C) 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.Pro142=

c.426T>C · rs2543604469 · VCV2786633

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 -8.9	GERP -4.9
Overall
CADD	0.176	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.Pro142=
Coding: c.426T>C
MANE Select: NM_000546
dbSNP: rs2543604469
Type: single nucleotide variant
Location: chr17:7675186 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 142: 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); a UniProt-annotated variant site (in sporadic cancers; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in a sporadic cancer; 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.Pro142Ala Uncertain significance ★★ ⚠ same residue
TP53 p.Pro142Ser Uncertain significance ★★ ⚠ same residue
TP53 p.Pro142Thr Uncertain significance ★★ ⚠ same residue
TP53 p.Pro142Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro142fs 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

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-pro142 (accessed [today's date]).

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