Is CREBBP p.Pro2152= (c.6456C>T) pathogenic?

CREBBP p.Pro2152= (c.6456C>T) is classified Likely benign in CREBBP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-05). Very rare (popmax 0.005%, amr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Pro2152= (c.6456C>T)?

CREBBP p.Pro2152= (c.6456C>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Pro2152= (c.6456C>T) in the general population?

CREBBP p.Pro2152= (c.6456C>T) is very rare (popmax 0.005%, amr) (gnomAD).

CREBBP p.Pro2152=

c.6456C>T · rs769799508 · VCV2052314

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -3.5
Overall
CADD	0.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00248% 40/1,613,704 alleles · very rare exomes 36/1,461,534 · genomes 4/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.0028%	35,756
African / African-American	0.00133%	74,920
South Asian	0.0011%	91,088

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CREBBP
Protein: p.Pro2152=
Coding: c.6456C>T
MANE Select: NM_004380
dbSNP: rs769799508
Type: single nucleotide variant
Location: chr16:3728591 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2152: the 'disordered' 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 p.Pro2152Ala Uncertain significance ★ ⚠ same residue
CREBBP p.Pro2152Ser 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
CREBBP p.Arg1233Lys 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-pro2152 (accessed [today's date]).

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