Is CREBBP p.Ile1823= (c.5469C>T) pathogenic?

CREBBP p.Ile1823= (c.5469C>T) is classified Likely benign in CREBBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-22). Ultra-rare (popmax 0.011%, sas); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ile1823= (c.5469C>T)?

CREBBP p.Ile1823= (c.5469C>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ile1823= (c.5469C>T) in the general population?

CREBBP p.Ile1823= (c.5469C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

CREBBP p.Ile1823=

c.5469C>T · rs757233262 · VCV1747703

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

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 -0.77	GERP -3.8
Overall
CADD	3.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,088 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00103% 15/1,461,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,109
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00223%	44,880
European (non-Finnish)	8.47e-05%	1,180,012

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.Ile1823=
Coding: c.5469C>T
MANE Select: NM_004380
dbSNP: rs757233262
Type: single nucleotide variant
Location: chr16:3729578 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1823: 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.Ile1823Phe 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-ile1823 (accessed [today's date]).

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