Is CREBBP p.Ser247Pro (c.739T>C) pathogenic?

CREBBP p.Ser247Pro (c.739T>C) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-01). AlphaMissense: likely benign (0.2159); Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ser247Pro (c.739T>C)?

CREBBP p.Ser247Pro (c.739T>C) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ser247Pro (c.739T>C) in the general population?

CREBBP p.Ser247Pro (c.739T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Ser247Pro (c.739T>C)?

AlphaMissense predicts likely benign (score 0.2159) — an in-silico prediction, not a clinical call.

CREBBP p.Ser247Pro

c.739T>C · rs2054804169 · VCV2757263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
AlphaMissense	0.2159	likely benign
REVEL	0.484	indeterminate
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 69 kb · p 0.4 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser247Pro
Coding: c.739T>C
MANE Select: NM_004380
dbSNP: rs2054804169
Type: single nucleotide variant
Location: chr16:3850356 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 247: 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 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
CREBBP p.Arg1867Gln 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-ser247pro (accessed [today's date]).

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