Is CREBBP p.Ser2283= (c.6849C>T) pathogenic?

CREBBP p.Ser2283= (c.6849C>T) is classified Benign/Likely benign in CREBBP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-25). Rare (popmax 0.846%, afr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ser2283= (c.6849C>T)?

CREBBP p.Ser2283= (c.6849C>T) is associated with Rubinstein-Taybi syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Menke-Hennekam syndrome 1 (ClinVar).

How common is CREBBP p.Ser2283= (c.6849C>T) in the general population?

CREBBP p.Ser2283= (c.6849C>T) is rare (popmax 0.846%, afr) (gnomAD).

CREBBP p.Ser2283=

c.6849C>T · rs148904096 · VCV498863

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.846%, 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 3.8	GERP -0.35, phastCons 1
Overall
CADD	5.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.846% African / African-American · 635/75,028 alleles

Filtering AF 0.792% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.77%

Overall 0.0546% 881/1,613,842 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.846%	118
Remaining individualsnot grpmax-eligible	0.0688%	1,454
Admixed American	0.045%	2,223
Middle Eastern	0.0331%	3,017
European (non-Finnish)	0.0142%	7,066
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
East Asian	0.00446%	22,440
South Asian	0.0011%	91,082

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.Ser2283=
Coding: c.6849C>T
MANE Select: NM_004380
dbSNP: rs148904096
Type: single nucleotide variant
Location: chr16:3728198 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB

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

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

Similar variants

CREBBP p.Ser2283Gly 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-ser2283 (accessed [today's date]).

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