Is CREBBP p.Pro1948= (c.5844G>A) pathogenic?

CREBBP p.Pro1948= (c.5844G>A) is classified Likely benign in CREBBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-22). Ultra-rare (popmax 0.0595%, eas); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Pro1948= (c.5844G>A)?

CREBBP p.Pro1948= (c.5844G>A) is associated with Rubinstein-Taybi syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Menke-Hennekam syndrome 1 (ClinVar).

How common is CREBBP p.Pro1948= (c.5844G>A) in the general population?

CREBBP p.Pro1948= (c.5844G>A) is ultra-rare (popmax 0.0595%, eas) (gnomAD).

CREBBP p.Pro1948=

c.5844G>A · rs537609194 · VCV3030138

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0595%, eas)

Conditions

Rubinstein-Taybi syndrome

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 -14	GERP -3.5
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0595% East Asian · 4/6,728 alleles

Filtering AF 0.0202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0122%

Overall 0.00434% 14/322,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0595%	1,682
South Asian	0.0175%	5,701
Remaining individualsnot grpmax-eligible	0.00895%	11,174
African / African-American	0.00425%	23,510
European (non-Finnish)	0.00138%	72,666

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.Pro1948=
Coding: c.5844G>A
MANE Select: NM_004380
dbSNP: rs537609194
Type: single nucleotide variant
Location: chr16:3729203 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1948: the 'disordered' region

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

Disease context

Rubinstein-Taybi syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to CREBBP mutations Menke-Hennekam syndrome 1

Similar variants

CREBBP p.Pro1948Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CREBBP p.Pro1948Thr Uncertain significance ★ ⚠ same residue
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3369+1G>T 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 c.3914+3G>T Likely 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-pro1948 (accessed [today's date]).

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