Is CREBBP p.Gln2188= (c.6564G>A) pathogenic?

CREBBP p.Gln2188= (c.6564G>A) is classified Benign/Likely benign in CREBBP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-06). Rare (popmax 0.673%, afr); Associated with Menke-Hennekam syndrome 1.

What condition is associated with CREBBP p.Gln2188= (c.6564G>A)?

CREBBP p.Gln2188= (c.6564G>A) is associated with Menke-Hennekam syndrome 1, Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Gln2188= (c.6564G>A) in the general population?

CREBBP p.Gln2188= (c.6564G>A) is rare (popmax 0.673%, afr) (gnomAD).

CREBBP p.Gln2188=

c.6564G>A · rs73491896 · VCV95061

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.673%, afr)

Conditions

Menke-Hennekam syndrome 1

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 1.4	GERP -1.4, phastCons 1
Overall
CADD	3.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.673% African / African-American · 505/75,026 alleles

Filtering AF 0.625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.605%

Overall 0.0351% 567/1,614,018 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.673%	149
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.0022%	45,541
European (non-Finnish)	0.000508%	196,667

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.Gln2188=
Coding: c.6564G>A
MANE Select: NM_004380
dbSNP: rs73491896
Type: single nucleotide variant
Location: chr16:3728483 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2188: the 'disordered' region

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

Disease context

Menke-Hennekam syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to CREBBP mutations Rubinstein-Taybi syndrome

Similar variants

CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3369+1G>T 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 c.3914+3G>T Likely pathogenic ★★ same condition
CREBBP c.3982+1G>A Pathogenic ★★ same condition
CREBBP p.Ala1782Thr 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-gln2188 (accessed [today's date]).

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