Is CREBBP p.Ser1778= (c.5334G>A) pathogenic?

CREBBP p.Ser1778= (c.5334G>A) is classified Conflicting classifications of pathogenicity in CREBBP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-29). Ultra-rare (popmax 0.028%, afr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ser1778= (c.5334G>A)?

CREBBP p.Ser1778= (c.5334G>A) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ser1778= (c.5334G>A) in the general population?

CREBBP p.Ser1778= (c.5334G>A) is ultra-rare (popmax 0.028%, afr) (gnomAD).

CREBBP p.Ser1778=

c.5334G>A · rs201062642 · VCV286953

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

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 -1.6	GERP -3.8
Overall
CADD	0.636	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/75,044 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00205% 33/1,611,330 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,574
Admixed American	0.00333%	29,994
Remaining individualsnot grpmax-eligible	0.0032%	31,230
East Asian	0.00223%	44,874
European (non-Finnish)	0.000593%	168,521

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.Ser1778=
Coding: c.5334G>A
MANE Select: NM_004380
dbSNP: rs201062642
Type: single nucleotide variant
Location: chr16:3729713 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1778: the 'interaction with trerf1' region; an α-helix

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

Similar variants

CREBBP p.Ser1778Leu Uncertain significance ★ ⚠ 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-ser1778 (accessed [today's date]).

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