Is CREBBP p.Arg1018fs (c.3054del) pathogenic?

CREBBP p.Arg1018fs (c.3054del) is classified Likely pathogenic in CREBBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-17). Associated with CREBBP-related disorder.

What condition is associated with CREBBP p.Arg1018fs (c.3054del)?

CREBBP p.Arg1018fs (c.3054del) is associated with CREBBP-related disorder (ClinVar).

CREBBP p.Arg1018fs

c.3054del · VCV3344477

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

CREBBP-related disorder

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 15 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -2.1, phastCons 0.097

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

Variant & gene context

Gene: CREBBP
Protein: p.Arg1018fs
Coding: c.3054del
MANE Select: NM_004380
Type: Deletion
Location: chr16:3769180 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1018: the 'disordered' region

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

Disease context

CREBBP-related disorder

Similar variants

CREBBP p.Gln1118fs Likely pathogenic ★ same condition
CREBBP p.Gln1700_Asp1701del Likely pathogenic ★ same condition
CREBBP p.Gly285fs Pathogenic ★ same condition
CREBBP p.Gly689fs Pathogenic ★ same condition
CREBBP p.Pro542fs Likely pathogenic ★ same condition
CREBBP p.Arg1018Gly Uncertain significance ★ ⚠ same residue
CREBBP p.Asp347_Pro348del Uncertain significance ★ same condition
CREBBP p.Ile1855_Gln1861del 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-arg1018fs (accessed [today's date]).

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