Is CREBBP p.Pro542fs (c.1625_1649del) pathogenic?

CREBBP p.Pro542fs (c.16251649del) is classified Likely pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-16). Absent from gnomAD; Associated with CREBBP-related disorder.

What condition is associated with CREBBP p.Pro542fs (c.1625_1649del)?

CREBBP p.Pro542fs (c.1625_1649del) is associated with CREBBP-related disorder (ClinVar).

How common is CREBBP p.Pro542fs (c.1625_1649del) in the general population?

CREBBP p.Pro542fs (c.1625_1649del) is absent from gnomAD (gnomAD).

CREBBP p.Pro542fs

c.1625_1649del · rs2141247434 · VCV1224416

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

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 7 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.5	GERP 0.11, 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.Pro542fs
Coding: c.1625_1649del
MANE Select: NM_004380
dbSNP: rs2141247434
Type: Deletion
Location: chr16:3781231 (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

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.Asp347_Pro348del Uncertain significance ★ same condition
CREBBP p.Ile1855_Gln1861del Uncertain significance ★ same condition
CREBBP p.Pro542His Uncertain significance ★ ⚠ same residue
CREBBP p.Thr1990_Gly1992del Conflicting classifications of pathogenicity ★ 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-pro542fs (accessed [today's date]).

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