Is CREBBP p.Val293= (c.879G>A) pathogenic?

CREBBP p.Val293= (c.879G>A) is classified Benign/Likely benign in CREBBP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0999%, mid); Associated with Rubinstein-Taybi syndrome due to CREBBP mutations.

What condition is associated with CREBBP p.Val293= (c.879G>A)?

CREBBP p.Val293= (c.879G>A) is associated with Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome, Menke-Hennekam syndrome 1 (ClinVar).

How common is CREBBP p.Val293= (c.879G>A) in the general population?

CREBBP p.Val293= (c.879G>A) is ultra-rare (popmax 0.0999%, mid) (gnomAD).

CREBBP p.Val293=

c.879G>A · rs144344016 · VCV458206

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, mid)

Conditions

Rubinstein-Taybi syndrome due to CREBBP mutations

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	GERP 1.2, phastCons 1
Overall
CADD	9.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0999% Middle Eastern · 6/6,008 alleles

Filtering AF 0.0684% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0628%

Overall 0.0553% 892/1,613,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0999%	1,001
South Asian	0.0835%	1,198
European (non-Finnish)	0.0608%	1,643
Remaining individualsnot grpmax-eligible	0.0592%	1,688
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
Finnishnot grpmax-eligible	0.0391%	2,560
African / African-American	0.0134%	7,485
Admixed American	0.01%	9,996

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.Val293=
Coding: c.879G>A
MANE Select: NM_004380
dbSNP: rs144344016
Type: single nucleotide variant
Location: chr16:3810699 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 293: the 'interaction with srcap' region

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

Disease context

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

Also linked: Rubinstein-Taybi syndrome Menke-Hennekam syndrome 1

Similar variants

CREBBP p.Val293Glu Uncertain significance ★ ⚠ same residue
CREBBP p.Val293Met 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-val293 (accessed [today's date]).

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