Is TP53 p.Pro191del (c.569CTC[1]) pathogenic?

TP53 p.Pro191del (c.569CTC[1]) is classified Pathogenic/Likely pathogenic in TP53 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-28). Absent from gnomAD; Associated with Li-Fraumeni syndrome.

What condition is associated with TP53 p.Pro191del (c.569CTC[1])?

TP53 p.Pro191del (c.569CTC[1]) is associated with Li-Fraumeni syndrome, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Pro191del (c.569CTC[1]) in the general population?

TP53 p.Pro191del (c.569CTC[1]) is absent from gnomAD (gnomAD).

How is Li-Fraumeni syndrome inherited?

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

TP53 p.Pro191del

c.569CTC[1] · rs1555525902 · VCV458551

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TP53
Protein: p.Pro191del
Coding: c.569CTC[1]
MANE Select: NM_000546
dbSNP: rs1555525902
Type: Microsatellite
Location: chr17:7674957 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 191: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; 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

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

For Li-Fraumeni syndrome (Orphanet):

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

Similar variants

TP53 p.Pro191Arg Likely benign ★★★ same residue
TP53 p.Pro191His Uncertain significance ★★ ⚠ same residue
TP53 p.Pro191Leu Uncertain significance ★ ⚠ same residue
TP53 p.Pro191Ser Uncertain significance ★ ⚠ same residue
TP53 p.Pro191= Likely benign ★ same residue
TP53 p.Asn30del Likely benign ★★★ same condition
TP53 p.Gln317fs Pathogenic ★★ same condition
TP53 p.Ile255del Pathogenic/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-pro191del (accessed [today's date]).

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