SETBP1 p.Pro1003=
c.3009G>A · rs142295785 · VCV1630213
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, sas)
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 4.2 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 13.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
South Asian · 45/91,068 alleles
Filtering AF
0.0379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0339%
Overall
0.0102%
164/1,614,034 alleles · ultra-rare
exomes 137/1,461,886 · genomes 27/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0494% | 2,024 |
| African / African-American | 0.0467% | 2,142 |
| European (non-Finnish) | 0.00661% | 15,129 |
| Admixed American | 0.005% | 20,003 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| East Asian | 0.00223% | 44,850 |
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.Pro1003=
- Coding
- c.3009G>A
- MANE Select
- NM_015559
- dbSNP
- rs142295785
- Type
- single nucleotide variant
- Location
- chr18:44952349 (GRCh38)
- Gene constraint
- LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.30
Similar variants
- 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
- SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same type
- SETBP1 p.Asp868His Pathogenic/Likely 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-pro1003 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown