Is CREBBP p.Ser1934Pro (c.5800T>C) pathogenic?

CREBBP p.Ser1934Pro (c.5800T>C) is classified Conflicting classifications of pathogenicity in CREBBP (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0875); Rare (popmax 0.135%, mid); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ser1934Pro (c.5800T>C)?

CREBBP p.Ser1934Pro (c.5800T>C) is associated with Rubinstein-Taybi syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations (ClinVar).

How common is CREBBP p.Ser1934Pro (c.5800T>C) in the general population?

CREBBP p.Ser1934Pro (c.5800T>C) is rare (popmax 0.135%, mid) (gnomAD).

What do computational predictors say about CREBBP p.Ser1934Pro (c.5800T>C)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

CREBBP p.Ser1934Pro

c.5800T>C · rs587783504 · VCV158387

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 568 bp · p 0.93 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% Middle Eastern · 6/4,446 alleles

Filtering AF 0.0588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.0375% 572/1,526,834 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.135%	741
Ashkenazi Jewishnot grpmax-eligible	0.134%	744
European (non-Finnish)	0.0426%	2,350
Remaining individualsnot grpmax-eligible	0.0353%	2,834
Admixed American	0.0138%	7,242
South Asian	0.0096%	10,422
African / African-American	0.00554%	18,041
Finnishnot grpmax-eligible	0.00448%	22,338

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.Ser1934Pro
Coding: c.5800T>C
MANE Select: NM_004380
dbSNP: rs587783504
Type: single nucleotide variant
Location: chr16:3729247 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1934: 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

Similar variants

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
CREBBP c.3982+1G>A Pathogenic ★★ same condition
CREBBP p.Ala1782Val Pathogenic/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-ser1934pro (accessed [today's date]).

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