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

CREBBP p.Pro295= (c.885C>T) is classified Benign/Likely benign in CREBBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-16). Very rare (popmax 0.00127%, nfe).

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

CREBBP p.Pro295= (c.885C>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

CREBBP p.Pro295=

c.885C>T · VCV3911145

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

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 0.69	GERP -4.4, phastCons 1
Overall
CADD	7.678	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,998 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00093% 15/1,613,770 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: CREBBP
Protein: p.Pro295=
Coding: c.885C>T
MANE Select: NM_004380
Type: single nucleotide variant
Location: chr16:3810693 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 295: the 'interaction with srcap' region

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

Similar variants

CREBBP p.Pro295Leu Uncertain significance ★ ⚠ same residue
CREBBP p.Pro295del Uncertain significance ★ same residue
CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3369+1G>T Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3779+1G>A Pathogenic ★★ same type
CREBBP c.3779+1G>T Pathogenic ★★ same type
CREBBP c.3836+1G>A Pathogenic ★★ same type

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/crebbp-p-pro295 (accessed [today's date]).

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