SETBP1 p.Ala34=
c.102A>C · rs572249525 · VCV1664548
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0782%, eas)
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 0.89 | GERP 1.3, phastCons 0.88 |
| Overall | ||
| CADD | 10.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0782%
East Asian · 35/44,766 alleles
Filtering AF
0.0577%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0507%
Overall
0.00236%
38/1,611,722 alleles · ultra-rare
exomes 35/1,459,498 · genomes 3/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0782% | 1,279 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,801 |
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.Ala34=
- Coding
- c.102A>C
- MANE Select
- NM_015559
- dbSNP
- rs572249525
- Type
- single nucleotide variant
- Location
- chr18:44701448 (GRCh38)
- Gene constraint
- LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.30
- Residue 34
- the 'disordered' region
Similar variants
- SETBP1 p.Ala34Ser Uncertain significance ★★ ⚠ same residue
- SETBP1 p.Ala34Val Uncertain significance ★ ⚠ same residue
- SETBP1 p.Arg530Ter Pathogenic ★★ same type
- SETBP1 p.Arg544Ter Pathogenic/Likely pathogenic ★★ same type
- SETBP1 p.Arg589Ter Pathogenic ★★ same type
- SETBP1 p.Arg625Ter Pathogenic ★★ same type
- SETBP1 p.Arg626Ter Pathogenic ★★ same type
- SETBP1 p.Arg889Ter Pathogenic ★★ 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/setbp1-p-ala34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown