Is CREBBP p.Arg768Ter (c.2302C>T) pathogenic?

CREBBP p.Arg768Ter (c.2302C>T) is classified Pathogenic in CREBBP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-22). Absent from gnomAD v4.1; Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Arg768Ter (c.2302C>T)?

CREBBP p.Arg768Ter (c.2302C>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Arg768Ter (c.2302C>T) in the general population?

CREBBP p.Arg768Ter (c.2302C>T) is absent from gnomAD v4.1 (gnomAD).

CREBBP p.Arg768Ter

c.2302C>T · rs1057520652 · VCV379578

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,196)

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 13 of 31
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.91 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,196). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CREBBP
Protein: p.Arg768Ter
Coding: c.2302C>T
MANE Select: NM_004380
dbSNP: rs1057520652
Type: single nucleotide variant
Location: chr16:3773912 (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 p.Arg768Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CREBBP p.Arg768= Likely benign ★ same residue
CREBBP p.Arg768Leu Uncertain significance ⚠ 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

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-arg768ter (accessed [today's date]).

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