Is CREBBP p.Pro867= (c.2601A>G) pathogenic?

CREBBP p.Pro867= (c.2601A>G) is classified Likely benign in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). Ultra-rare (popmax 0.0174%, afr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Pro867= (c.2601A>G)?

CREBBP p.Pro867= (c.2601A>G) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Pro867= (c.2601A>G) in the general population?

CREBBP p.Pro867= (c.2601A>G) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

CREBBP p.Pro867=

c.2601A>G · rs773476527 · VCV2085479

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Conditions

Rubinstein-Taybi 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 -10	GERP -3.5
Overall
CADD	0.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,798 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00814%

Overall 0.00118% 19/1,613,676 alleles · ultra-rare exomes 15/1,461,820 · genomes 4/151,856 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,754
European (non-Finnish)	0.000508%	196,661

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.Pro867=
Coding: c.2601A>G
MANE Select: NM_004380
dbSNP: rs773476527
Type: single nucleotide variant
Location: chr16:3770849 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 867: the 'disordered' region

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

Disease context

Rubinstein-Taybi syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3779+1G>A Pathogenic ★★ same condition
CREBBP c.3779+1G>T Pathogenic ★★ same condition
CREBBP c.3836+1G>A Pathogenic ★★ same condition
CREBBP p.Arg1103Ter Pathogenic ★★ same condition
CREBBP p.Arg1233Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg1498Ter Pathogenic ★★ same condition
CREBBP p.Arg1867Gln 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/crebbp-p-pro867 (accessed [today's date]).

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