Is TP53 p.Pro64= (c.192C>T) pathogenic?

TP53 p.Pro64= (c.192C>T) is classified Likely benign in TP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-28). Very rare (popmax 0.0011%, sas); Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Pro64= (c.192C>T)?

TP53 p.Pro64= (c.192C>T) is associated with Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Pro64= (c.192C>T) in the general population?

TP53 p.Pro64= (c.192C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Li-Fraumeni syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TP53 p.Pro64=

c.192C>T · rs1555526723 · VCV3069241

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -0.21	GERP -4.1
Overall
CADD	3.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 6.84e-05% 1/1,461,798 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.Pro64=
Coding: c.192C>T
MANE Select: NM_000546
dbSNP: rs1555526723
Type: single nucleotide variant
Location: chr17:7676177 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 64: the 'interaction with ccar2' region; the 'interaction with hrmt1l2' region; the 'disordered' 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.Pro64Ser Uncertain significance ★★ ⚠ same residue
TP53 p.Pro64Leu Uncertain significance ★ ⚠ same residue
TP53 p.Pro64Thr Uncertain significance ★ ⚠ same residue
TP53 p.Pro64fs 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
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-pro64 (accessed [today's date]).

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