Is CREBBP p.Pro2018= (c.6054C>T) pathogenic?

CREBBP p.Pro2018= (c.6054C>T) is classified Likely benign in CREBBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-27). Very rare (popmax 0.00512%, amr); Associated with Inborn genetic diseases.

What condition is associated with CREBBP p.Pro2018= (c.6054C>T)?

CREBBP p.Pro2018= (c.6054C>T) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Pro2018= (c.6054C>T) in the general population?

CREBBP p.Pro2018= (c.6054C>T) is very rare (popmax 0.00512%, amr) (gnomAD).

CREBBP p.Pro2018=

c.6054C>T · rs768626011 · VCV772272

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00512%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -3.5
Overall
CADD	1.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00512% Admixed American · 3/58,636 alleles

Filtering AF 0.00136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000676%

Overall 0.00144% 23/1,594,890 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00512%	19,545
Remaining individualsnot grpmax-eligible	0.00484%	20,656
East Asian	0.0045%	22,223
African / African-American	0.00268%	37,374
European (non-Finnish)	0.00111%	90,479

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CREBBP
Protein: p.Pro2018=
Coding: c.6054C>T
MANE Select: NM_004380
dbSNP: rs768626011
Type: single nucleotide variant
Location: chr16:3728993 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2018: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome

Similar variants

CREBBP p.Pro2018Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3779+1G>A Pathogenic ★★ same condition
CREBBP c.3779+1G>T Pathogenic ★★ same condition
CREBBP c.3836+1G>A Pathogenic ★★ same condition
CREBBP p.Arg1103Ter Pathogenic ★★ same condition
CREBBP p.Arg1233Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg1498Ter 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-pro2018 (accessed [today's date]).

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