Is CREBBP p.Ile678= (c.2034C>T) pathogenic?

CREBBP p.Ile678= (c.2034C>T) is classified Conflicting classifications of pathogenicity in CREBBP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-23). Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ile678= (c.2034C>T)?

CREBBP p.Ile678= (c.2034C>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ile678= (c.2034C>T) in the general population?

CREBBP p.Ile678= (c.2034C>T) is absent from gnomAD v4.1 (gnomAD).

CREBBP p.Ile678=

c.2034C>T · rs398124141 · VCV95030

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 4.5	GERP 1.9, phastCons 1
Overall
CADD	9.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CREBBP
Protein: p.Ile678=
Coding: c.2034C>T
MANE Select: NM_004380
dbSNP: rs398124141
Type: single nucleotide variant
Location: chr16:3778090 (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.Ile678Met Uncertain significance ★ ⚠ same residue
CREBBP c.2881-13G>A 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 p.Arg1103Ter Pathogenic ★★ same condition
CREBBP p.Arg1233Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg1498Ter 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-ile678 (accessed [today's date]).

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