Is CREBBP p.Pro700Ser (c.2098C>T) pathogenic?

CREBBP p.Pro700Ser (c.2098C>T) is classified Uncertain significance in CREBBP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-23). AlphaMissense: likely benign (0.0576); Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Pro700Ser (c.2098C>T)?

CREBBP p.Pro700Ser (c.2098C>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Pro700Ser (c.2098C>T) in the general population?

CREBBP p.Pro700Ser (c.2098C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Pro700Ser (c.2098C>T)?

AlphaMissense predicts likely benign (score 0.0576) — an in-silico prediction, not a clinical call.

CREBBP p.Pro700Ser

c.2098C>T · rs2053186121 · VCV2102606

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0576 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
AlphaMissense	0.0576	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -7.24	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 2.3	GERP -0.34, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.52 · regional, not allelic
Overall
CADD	17.58	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.Pro700Ser
Coding: c.2098C>T
MANE Select: NM_004380
dbSNP: rs2053186121
Type: single nucleotide variant
Location: chr16:3778026 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB

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-pro700ser (accessed [today's date]).

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