CREBBP p.Leu2139=
c.6417G>A · rs748399111 · VCV2055693
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
Rubinstein-Taybi syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.23 | GERP 1.9, phastCons 0.98 |
| Overall | ||
| CADD | 3.496 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,870 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000558%
9/1,613,530 alleles · very rare
exomes 7/1,461,380 · genomes 2/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,435 |
| Admixed American | 0.00333% | 29,995 |
| African / African-American | 0.00267% | 37,457 |
| European (non-Finnish) | 0.000254% | 393,303 |
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.Leu2139=
- Coding
- c.6417G>A
- MANE Select
- NM_004380
- dbSNP
- rs748399111
- Type
- single nucleotide variant
- Location
- chr16:3728630 (GRCh38)
- Gene constraint
- LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.31 · 144 PDB
- Residue 2139
- 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-leu2139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown