Is CREBBP p.Met2016fs (c.6046_6049del) pathogenic?

CREBBP p.Met2016fs (c.60466049del) is classified Likely pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). Associated with Rubinstein-Taybi syndrome due to CREBBP mutations.

What condition is associated with CREBBP p.Met2016fs (c.6046_6049del)?

CREBBP p.Met2016fs (c.6046_6049del) is associated with Rubinstein-Taybi syndrome due to CREBBP mutations (ClinVar).

CREBBP p.Met2016fs

c.6046_6049del · VCV3381256

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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	escapes	premature termination codon in the last exon (31 of 31) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.3	GERP 0.78, phastCons 1

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

Variant & gene context

Gene: CREBBP
Protein: p.Met2016fs
Coding: c.6046_6049del
MANE Select: NM_004380
Type: Deletion
Location: chr16:3728998 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2016: 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 c.3369+1del Pathogenic ★★ same condition
CREBBP p.Ala403fs Likely pathogenic ★★ same condition
CREBBP p.Glu1034fs Pathogenic ★★ same condition
CREBBP p.Glu1551fs 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.Pro1077del 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-met2016fs (accessed [today's date]).

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