Is CREBBP p.Pro696fs (c.2085del) pathogenic?

CREBBP p.Pro696fs (c.2085del) is classified Likely pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). Absent from gnomAD.

How common is CREBBP p.Pro696fs (c.2085del) in the general population?

CREBBP p.Pro696fs (c.2085del) is absent from gnomAD (gnomAD).

CREBBP p.Pro696fs

c.2085del · rs2548431236 · VCV2575956

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 10 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.1	GERP 1.9, 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.Pro696fs
Coding: c.2085del
MANE Select: NM_004380
dbSNP: rs2548431236
Type: Deletion
Location: chr16:3778039 (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

Similar variants

CREBBP c.3369+1del Pathogenic ★★ same type
CREBBP p.Ala403fs Likely pathogenic ★★ same type
CREBBP p.Glu1034fs Pathogenic ★★ same type
CREBBP p.Glu1551fs Pathogenic ★★ same type
CREBBP p.Glu1560fs Pathogenic ★★ same type
CREBBP p.Pro1946fs Pathogenic/Likely pathogenic ★★ same type
CREBBP p.Ser1898fs Pathogenic/Likely pathogenic ★★ same type
CREBBP p.Gln2128_Met2133del Uncertain significance ★★ same type

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-pro696fs (accessed [today's date]).

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