Is TP53 p.Pro13Leu (c.38C>T) pathogenic?

TP53 p.Pro13Leu (c.38C>T) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1938); Very rare (popmax 0.00134%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Pro13Leu (c.38C>T)?

TP53 p.Pro13Leu (c.38C>T) is associated with hereditary neoplastic syndrome, adrenocortical carcinoma, hereditary, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Pro13Leu (c.38C>T) in the general population?

TP53 p.Pro13Leu (c.38C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about TP53 p.Pro13Leu (c.38C>T)?

AlphaMissense predicts likely benign (score 0.1938) — an in-silico prediction, not a clinical call.

TP53 p.Pro13Leu

c.38C>T · rs878854070 · VCV237949

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1938	likely benign
REVEL	0.769	pathogenic-leaning
SaProt	LLR -5.50	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.00134% African / African-American · 1/74,896 alleles

Overall 0.000657% 1/152,146 alleles · very rare

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.Pro13Leu
Coding: c.38C>T
MANE Select: NM_000546
dbSNP: rs878854070
Type: single nucleotide variant
Location: chr17:7676557 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 13: the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'transcription activation (acidic)' 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: adrenocortical carcinoma, hereditary Li-Fraumeni syndrome

Similar variants

TP53 p.Pro13Ser Uncertain significance ★★★ ⚠ same residue
TP53 p.Pro13= Benign/Likely benign ★★ same residue
TP53 p.Pro13Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro13Arg Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro13leu (accessed [today's date]).

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