Is CREBBP p.Thr251= (c.753T>G) pathogenic?

CREBBP p.Thr251= (c.753T>G) is classified Benign/Likely benign in CREBBP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.34%, afr); Associated with Rubinstein-Taybi syndrome due to CREBBP mutations.

What condition is associated with CREBBP p.Thr251= (c.753T>G)?

CREBBP p.Thr251= (c.753T>G) is associated with Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome, Menke-Hennekam syndrome 1 (ClinVar).

How common is CREBBP p.Thr251= (c.753T>G) in the general population?

CREBBP p.Thr251= (c.753T>G) is rare (popmax 0.34%, afr) (gnomAD).

CREBBP p.Thr251=

c.753T>G · rs142403441 · VCV95068

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.34%, afr)

Conditions

Rubinstein-Taybi syndrome due to CREBBP mutations

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.3	GERP -4.8, phastCons 0.002
Overall
CADD	1.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.34% African / African-American · 255/75,064 alleles

Filtering AF 0.305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.292%

Overall 0.0169% 273/1,614,246 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.34%	294
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.0117%	8,576

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.Thr251=
Coding: c.753T>G
MANE Select: NM_004380
dbSNP: rs142403441
Type: single nucleotide variant
Location: chr16:3850342 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 251: the 'interaction with srcap' region

Full CREBBP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rubinstein-Taybi syndrome due to CREBBP mutations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome Menke-Hennekam syndrome 1

Similar variants

CREBBP p.Thr251Ser Uncertain significance ★ ⚠ 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-thr251 (accessed [today's date]).

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