CREBBP p.Pro2117=
c.6351C>T · rs142846349 · VCV1251900
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, afr)
Conditions
1
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 0.83 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 5.415 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
African / African-American · 37/75,060 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0323%
Overall
0.00242%
39/1,614,002 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0493% | 2,029 |
| Admixed American | 0.00333% | 30,015 |
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.Pro2117=
- Coding
- c.6351C>T
- MANE Select
- NM_004380
- dbSNP
- rs142846349
- Type
- single nucleotide variant
- Location
- chr16:3728696 (GRCh38)
- Gene constraint
- LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.31 · 144 PDB
- Residue 2117
- the 'disordered' region
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-pro2117 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown