Is CREBBP p.Phe1632Val (c.4894T>G) pathogenic?

CREBBP p.Phe1632Val (c.4894T>G) is classified Conflicting classifications of pathogenicity in CREBBP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-04). AlphaMissense: likely pathogenic (0.9944); Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome due to CREBBP mutations.

What condition is associated with CREBBP p.Phe1632Val (c.4894T>G)?

CREBBP p.Phe1632Val (c.4894T>G) is associated with Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Phe1632Val (c.4894T>G) in the general population?

CREBBP p.Phe1632Val (c.4894T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Phe1632Val (c.4894T>G)?

AlphaMissense predicts likely pathogenic (score 0.9944) — an in-silico prediction, not a clinical call.

CREBBP p.Phe1632Val

c.4894T>G · rs587783501 · VCV2790125

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Rubinstein-Taybi syndrome due to CREBBP mutations

Computational evidence

Protein change
AlphaMissense	0.9944	likely pathogenic
REVEL	0.96	strongly pathogenic-leaning
SaProt	LLR -14.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 5,241 bp · p 7e-08 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CREBBP
Protein: p.Phe1632Val
Coding: c.4894T>G
MANE Select: NM_004380
dbSNP: rs587783501
Type: single nucleotide variant
Location: chr16:3731470 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1632: the 'interaction with trerf1' region; the cbp/p300-type hat domain

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

Similar variants

CREBBP p.Phe1632Leu Uncertain significance ★ ⚠ same residue
CREBBP p.Phe1632= Likely benign 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-phe1632val (accessed [today's date]).

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