Is CREBBP p.Ala234Val (c.701C>T) pathogenic?

CREBBP p.Ala234Val (c.701C>T) is classified Likely benign in CREBBP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-20). AlphaMissense: likely benign (0.1142); Ultra-rare (popmax 0.0167%, amr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ala234Val (c.701C>T)?

CREBBP p.Ala234Val (c.701C>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ala234Val (c.701C>T) in the general population?

CREBBP p.Ala234Val (c.701C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about CREBBP p.Ala234Val (c.701C>T)?

AlphaMissense predicts likely benign (score 0.1142) — an in-silico prediction, not a clinical call.

CREBBP p.Ala234Val

c.701C>T · rs727503892 · VCV166966

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1142 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
AlphaMissense	0.1142	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 69 kb · p 0.4 · regional, not allelic
Overall
CADD	23.4	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 0.0167% Admixed American · 10/60,010 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.000743% 12/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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.Ala234Val
Coding: c.701C>T
MANE Select: NM_004380
dbSNP: rs727503892
Type: single nucleotide variant
Location: chr16:3850394 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 234: the 'interaction with srcap' 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.Ala234Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CREBBP p.Ala234= Likely benign ★ 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-ala234val (accessed [today's date]).

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