Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.57%, afr)
Conditions
1
Schinzel-Giedion 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 -0.71 | GERP -2.7 |
| Overall | ||
| CADD | 3.971 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.57%
African / African-American · 1,177/75,030 alleles
Filtering AF
1.49%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.46%
Overall
0.08%
1,291/1,614,062 alleles · low-frequency
exomes 636/1,461,802 · genomes 655/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.57% | 64 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| Admixed American | 0.0817% | 1,225 |
| South Asian | 0.00549% | 18,215 |
| East Asian | 0.00223% | 44,866 |
| European (non-Finnish) | 0.000508% | 196,671 |
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
- SETBP1
- Protein
- p.Ala390=
- Coding
- c.1170C>T
- MANE Select
- NM_015559
- dbSNP
- rs8091231
- Type
- single nucleotide variant
- Location
- chr18:44950510 (GRCh38)
- Gene constraint
- LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.30
- Residue 390
- the 'disordered' region
Similar variants
- SETBP1 p.Ala390Ser Uncertain significance ★ ⚠ same residue
- SETBP1 p.Arg589Ter Pathogenic ★★ same condition
- SETBP1 p.Arg625Ter Pathogenic ★★ same condition
- SETBP1 p.Arg626Ter Pathogenic ★★ same condition
- SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same condition
- SETBP1 p.Asp868His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SETBP1 p.Glu858Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SETBP1 p.Gly870Asp 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/setbp1-p-ala390 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown