Is CREBBP p.Pro813fs (c.2436_2437insGCTG) pathogenic?

CREBBP p.Pro813fs (c.24362437insGCTG) is classified Pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-01). Absent from gnomAD; Associated with Rubinstein-Taybi syndrome due to CREBBP mutations.

What condition is associated with CREBBP p.Pro813fs (c.2436_2437insGCTG)?

CREBBP p.Pro813fs (c.2436_2437insGCTG) is associated with Rubinstein-Taybi syndrome due to CREBBP mutations (ClinVar).

How common is CREBBP p.Pro813fs (c.2436_2437insGCTG) in the general population?

CREBBP p.Pro813fs (c.2436_2437insGCTG) is absent from gnomAD (gnomAD).

CREBBP p.Pro813fs

c.2436_2437insGCTG · rs2141214738 · VCV1684276

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 due to CREBBP mutations

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 13 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 0.67, 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.Pro813fs
Coding: c.2436_2437insGCTG
MANE Select: NM_004380
dbSNP: rs2141214738
Type: Insertion
Location: chr16:3773777 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 813: the 'disordered' region

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

Disease context

Rubinstein-Taybi syndrome due to CREBBP mutations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CREBBP p.Pro813= Likely benign ★★ same residue
CREBBP p.Ser1980fs Pathogenic ★ same condition
CREBBP p.Pro813Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CREBBP p.Pro813Ser Uncertain significance ★ ⚠ same residue
CREBBP p.His1487fs Pathogenic same condition
CREBBP p.Ile82Ter Pathogenic same condition
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3369+1del 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-pro813fs (accessed [today's date]).

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