Is TP53 p.Pro295= (c.885T>C) pathogenic?

TP53 p.Pro295= (c.885T>C) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00314%, nfe); Associated with familial pancreatic carcinoma.

What condition is associated with TP53 p.Pro295= (c.885T>C)?

TP53 p.Pro295= (c.885T>C) is associated with familial pancreatic carcinoma, head and neck squamous cell carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Pro295= (c.885T>C) in the general population?

TP53 p.Pro295= (c.885T>C) is very rare (popmax 0.00314%, nfe) (gnomAD).

How is Familial pancreatic carcinoma inherited?

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

TP53 p.Pro295=

c.885T>C · rs200073907 · VCV132754

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

familial pancreatic carcinoma

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 1.1	GERP -2.1, phastCons 0.098
Overall
CADD	5.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,180,032 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00235% 38/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,893
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Pro295=
Coding: c.885T>C
MANE Select: NM_000546
dbSNP: rs200073907
Type: single nucleotide variant
Location: chr17:7673735 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 295: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'disordered' region; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial pancreatic carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: head and neck squamous cell carcinoma hereditary neoplastic syndrome Li-Fraumeni syndrome

For Familial pancreatic carcinoma (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TP53 p.Pro295Ser Likely benign ★★★ same residue
TP53 p.Pro295Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Pro295fs Pathogenic ★ same residue
TP53 p.Pro295His Uncertain significance ★ ⚠ 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-pro295 (accessed [today's date]).

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