Is CREBBP p.Gln355fs (c.1063_1064del) pathogenic?

CREBBP p.Gln355fs (c.10631064del) is classified Pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-11). Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Gln355fs (c.1063_1064del)?

CREBBP p.Gln355fs (c.1063_1064del) is associated with Rubinstein-Taybi syndrome (ClinVar).

CREBBP p.Gln355fs

c.1063_1064del · VCV4735055

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 4 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 2.5, phastCons 1

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

Variant & gene context

Gene: CREBBP
Protein: p.Gln355fs
Coding: c.1063_1064del
MANE Select: NM_004380
Type: Deletion
Location: chr16:3793538 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 355: the 'interaction with srcap' 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 p.Gln355Ter Pathogenic ★★ same residue
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

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-gln355fs (accessed [today's date]).

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