Is CREBBP p.Ser1687Phe (c.5060C>T) pathogenic?

CREBBP p.Ser1687Phe (c.5060C>T) is classified Likely pathogenic in CREBBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-31). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Ser1687Phe (c.5060C>T)?

CREBBP p.Ser1687Phe (c.5060C>T) is associated with Rubinstein-Taybi syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Menke-Hennekam syndrome 1 (ClinVar).

How common is CREBBP p.Ser1687Phe (c.5060C>T) in the general population?

CREBBP p.Ser1687Phe (c.5060C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Ser1687Phe (c.5060C>T)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

CREBBP p.Ser1687Phe

c.5060C>T · rs2151316542 · VCV1066341

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 4% in CREBBP
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -12.16	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 1,647 bp · p 4.8e-14 · regional, not allelic
Overall
CADD	25.8	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.Ser1687Phe
Coding: c.5060C>T
MANE Select: NM_004380
dbSNP: rs2151316542
Type: single nucleotide variant
Location: chr16:3731304 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1687: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to CREBBP mutations Menke-Hennekam syndrome 1

Similar variants

CREBBP p.Ser1687Pro Likely pathogenic ★ 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
CREBBP c.3982+1G>A 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-ser1687phe (accessed [today's date]).

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