Is CREBBP p.Lys16fs (c.47_48delinsT) pathogenic?

CREBBP p.Lys16fs (c.4748delinsT) is classified Pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-22). Absent from gnomAD; Associated with Rubinstein-Taybi syndrome due to CREBBP mutations.

What condition is associated with CREBBP p.Lys16fs (c.47_48delinsT)?

CREBBP p.Lys16fs (c.47_48delinsT) is associated with Rubinstein-Taybi syndrome due to CREBBP mutations (ClinVar).

How common is CREBBP p.Lys16fs (c.47_48delinsT) in the general population?

CREBBP p.Lys16fs (c.47_48delinsT) is absent from gnomAD (gnomAD).

CREBBP p.Lys16fs

c.47_48delinsT · rs2055490250 · VCV1029838

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 1 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.5	GERP 1.6, 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.Lys16fs
Coding: c.47_48delinsT
MANE Select: NM_004380
dbSNP: rs2055490250
Type: Indel
Location: chr16:3879869 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 16: 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.Gln2303_Gln2304delinsHisLys Uncertain significance ★★ same condition
CREBBP c.4395-3_4395-1delinsTCAC Pathogenic ★ same condition
CREBBP p.Asn563fs Pathogenic ★ same condition
CREBBP p.Asp1127fs Pathogenic ★ same condition
CREBBP p.Leu1026_Ala1029delinsTer Pathogenic ★ same condition
CREBBP p.Met1988fs Likely pathogenic ★ same condition
CREBBP p.Ser894fs Pathogenic ★ same condition
CREBBP p.Ala940fs 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-lys16fs (accessed [today's date]).

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