Is CREBBP p.Ala15= (c.45C>G) pathogenic?

CREBBP p.Ala15= (c.45C>G) is classified Benign in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Very rare (popmax 0.00167%, amr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ala15= (c.45C>G)?

CREBBP p.Ala15= (c.45C>G) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ala15= (c.45C>G) in the general population?

CREBBP p.Ala15= (c.45C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

CREBBP p.Ala15=

c.45C>G · rs1406200900 · VCV2962984

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 5.8	GERP 1.6, phastCons 1
Overall
CADD	14.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,920 alleles

Overall 0.000124% 2/1,612,476 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,920
African / African-American	0.00134%	74,834

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.Ala15=
Coding: c.45C>G
MANE Select: NM_004380
dbSNP: rs1406200900
Type: single nucleotide variant
Location: chr16:3879872 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 15: 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

Similar variants

CREBBP p.Ala15Gly Uncertain significance ★★ ⚠ same residue
CREBBP p.Ala15Thr 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

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-ala15 (accessed [today's date]).

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