SETDB1 p.Ala1128=
c.3384G>A · rs145830865 · VCV2639165
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, afr)
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 -4.2 | GERP -3 |
| Overall | ||
| CADD | 1.946 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
African / African-American · 13/74,916 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00813%
Overall
0.00341%
55/1,614,050 alleles · ultra-rare
exomes 44/1,461,876 · genomes 11/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0174% | 5,763 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| Admixed American | 0.00333% | 29,997 |
| European (non-Finnish) | 0.0028% | 35,759 |
| South Asian | 0.0011% | 91,090 |
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
- SETDB1
- Protein
- p.Ala1128=
- Coding
- c.3384G>A
- MANE Select
- NM_001366418
- dbSNP
- rs145830865
- Type
- single nucleotide variant
- Location
- chr1:150963063 (GRCh38)
- Gene constraint
- LOEUF 0.29 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.45 · 26 PDB
- Residue 1128
- the 'disordered' region; the set domain
Similar variants
- SETDB1 c.261-3T>C Likely benign ★★ same type
- SETDB1 p.Ala1022Val Benign ★★ same type
- SETDB1 p.Pro469= Benign ★★ same type
- SETDB1 p.Pro530Leu Benign/Likely benign ★★ same type
- SETDB1 p.Pro978Leu Likely benign ★★ same type
- SETDB1 c.674-2A>G Uncertain significance ★ same type
- SETDB1 p.Arg1244Leu Uncertain significance ★ ⚠ same type
- SETDB1 p.Arg611Gln Uncertain significance ★ ⚠ same type
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/setdb1-p-ala1128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown