CREBBP p.Ser2076=
c.6228G>A · rs759497776 · VCV596124
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 -11 | GERP -3.8 |
| Overall | ||
| CADD | 1.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,086 alleles
Filtering AF
0.00207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00183%
Overall
0.00279%
45/1,613,476 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,772 |
| African / African-American | 0.004% | 24,980 |
| Admixed American | 0.00333% | 30,006 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| European (non-Finnish) | 0.00288% | 34,706 |
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.Ser2076=
- Coding
- c.6228G>A
- MANE Select
- NM_004380
- dbSNP
- rs759497776
- Type
- single nucleotide variant
- Location
- chr16:3728819 (GRCh38)
- Gene constraint
- LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.31 · 144 PDB
- Residue 2076
- a modified residue (phosphoserine)
Similar variants
- CREBBP p.Ser2076Ter Pathogenic ★ same residue
- CREBBP p.Ser2076Leu 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-ser2076 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown