Is CREBBP p.Ser745fs (c.2233del) pathogenic?

CREBBP p.Ser745fs (c.2233del) is classified Pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-16). Absent from gnomAD; Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ser745fs (c.2233del)?

CREBBP p.Ser745fs (c.2233del) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ser745fs (c.2233del) in the general population?

CREBBP p.Ser745fs (c.2233del) is absent from gnomAD (gnomAD).

CREBBP p.Ser745fs

c.2233del · rs2053092574 · VCV943635

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CREBBP
Protein: p.Ser745fs
Coding: c.2233del
MANE Select: NM_004380
dbSNP: rs2053092574
Type: Deletion
Location: chr16:3774619 (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

Similar variants

CREBBP p.Glu1034fs Pathogenic ★★ same condition
CREBBP p.Glu1560fs Pathogenic ★★ same condition
CREBBP p.Pro1946fs Pathogenic/Likely pathogenic ★★ same condition
CREBBP p.Ser1898fs Pathogenic/Likely pathogenic ★★ same condition
CREBBP p.Gln2128_Met2133del Uncertain significance ★★ same condition
CREBBP p.Gln2206_Gln2216del Uncertain significance ★★ same condition
CREBBP p.Gln2211_Gln2216del Uncertain significance ★★ same condition
CREBBP p.Gly1015del Uncertain significance ★★ 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-ser745fs (accessed [today's date]).

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