SETBP1 p.Pro230=
c.690C>T · rs377615601 · VCV1641845
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
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 -2.7 | GERP -5.4 |
| Overall | ||
| CADD | 4.651 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,088 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00118%
19/1,614,060 alleles · ultra-rare
exomes 17/1,461,852 · genomes 2/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,281 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| African / African-American | 0.00267% | 37,465 |
| East Asian | 0.00223% | 44,898 |
| European (non-Finnish) | 0.000254% | 393,338 |
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.Pro230=
- Coding
- c.690C>T
- MANE Select
- NM_015559
- dbSNP
- rs377615601
- Type
- single nucleotide variant
- Location
- chr18:44950030 (GRCh38)
- Gene constraint
- LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.30
- Residue 230
- the 'disordered' region
Similar variants
- SETBP1 p.Pro230His Uncertain significance ★ ⚠ same residue
- SETBP1 p.Pro230Thr Benign ★ 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-pro230 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown