Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 17.1%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
2
Inborn genetic diseases
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 -9.4 | GERP -3.5 |
| Overall | ||
| CADD | 0.439 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17.1%
East Asian · 7,675/44,862 alleles
Filtering AF
16.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 16.7%
Overall
1.59%
25,668/1,613,890 alleles · common
exomes 22,175/1,461,764 · genomes 3,493/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 17.1% | 6 |
| South Asian | 11.2% | 9 |
| African / African-American | 3.36% | 30 |
| Amishnot grpmax-eligible | 3.07% | 33 |
| Remaining individualsnot grpmax-eligible | 2.46% | 41 |
| Middle Eastern | 2.39% | 42 |
| Admixed American | 1.16% | 87 |
| Ashkenazi Jewishnot grpmax-eligible | 0.618% | 162 |
| European (non-Finnish) | 0.218% | 459 |
| Finnishnot grpmax-eligible | 0.214% | 467 |
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.Pro928=
- Coding
- c.2784G>A
- MANE Select
- NM_004380
- dbSNP
- rs3025694
- Type
- single nucleotide variant
- Location
- chr16:3770666 (GRCh38)
- Gene constraint
- LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.31 · 144 PDB
- Residue 928
- the 'disordered' region
Similar variants
- CREBBP p.Pro928Leu Likely benign ★ 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
- CREBBP p.Arg1498Ter 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-pro928 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown