Is CREBBP p.Pro800= (c.2400G>A) pathogenic?

CREBBP p.Pro800= (c.2400G>A) is classified Likely benign in CREBBP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-23). Very rare (popmax 0.00729%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CREBBP p.Pro800= (c.2400G>A)?

CREBBP p.Pro800= (c.2400G>A) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Pro800= (c.2400G>A) in the general population?

CREBBP p.Pro800= (c.2400G>A) is very rare (popmax 0.00729%, nfe) (gnomAD).

CREBBP p.Pro800=

c.2400G>A · rs756570921 · VCV730758

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Conditions

Inborn genetic diseases

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 -9.5	GERP -3.6
Overall
CADD	6.605	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,180,032 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00595% 96/1,613,102 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,721
African / African-American	0.00534%	18,724
Admixed American	0.00333%	30,001
South Asian	0.0033%	30,346
Remaining individualsnot grpmax-eligible	0.0016%	62,388

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.Pro800=
Coding: c.2400G>A
MANE Select: NM_004380
dbSNP: rs756570921
Type: single nucleotide variant
Location: chr16:3773814 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 800: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to CREBBP mutations Rubinstein-Taybi syndrome Menke-Hennekam syndrome 1

Similar variants

CREBBP p.Pro800Leu Uncertain significance ★★ ⚠ same residue
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

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-pro800 (accessed [today's date]).

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