Is TP53 p.Pro80Leu (c.239C>T) pathogenic?

TP53 p.Pro80Leu (c.239C>T) is classified Uncertain significance in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-11). AlphaMissense: likely benign (0.0939); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro80Leu (c.239C>T)?

TP53 p.Pro80Leu (c.239C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Pro80Leu (c.239C>T) in the general population?

TP53 p.Pro80Leu (c.239C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Pro80Leu (c.239C>T)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

TP53 p.Pro80Leu

c.239C>T · rs2151041185 · VCV1790682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.419	indeterminate
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.65, phastCons 0.55
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	8.463	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.Pro80Leu
Coding: c.239C>T
MANE Select: NM_000546
dbSNP: rs2151041185
Type: single nucleotide variant
Location: chr17:7676130 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 80: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' region; the 'interaction with wwox' 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

Similar variants

TP53 p.Pro80Ser Uncertain significance ★★ ⚠ same residue
TP53 p.Pro80= Benign ★ 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
TP53 p.Ala347Asp 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-pro80leu (accessed [today's date]).

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