SETBP1 p.Ser228=
c.684C>T · rs149073567 · VCV1219390
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.04%, afr)
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 1.2 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 7.542 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.04%
African / African-American · 30/75,048 alleles
Filtering AF
0.0288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.0062%
100/1,614,160 alleles · ultra-rare
exomes 73/1,461,824 · genomes 27/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.04% | 2,502 |
| Middle Eastern | 0.033% | 3,031 |
| Finnishnot grpmax-eligible | 0.0266% | 3,765 |
| Admixed American | 0.02% | 5,002 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,628 |
| European (non-Finnish) | 0.00288% | 34,706 |
| South Asian | 0.0011% | 91,082 |
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.Ser228=
- Coding
- c.684C>T
- MANE Select
- NM_015559
- dbSNP
- rs149073567
- Type
- single nucleotide variant
- Location
- chr18:44950024 (GRCh38)
- Gene constraint
- LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.30
- Residue 228
- the 'disordered' region
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-ser228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown