CAPS2 p.Glu189=
c.567G>A · rs35198123 · VCV783668
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.06%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.81 | GERP -3.3, phastCons 0.02 |
| Overall | ||
| CADD | 1.709 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.06%
African / African-American · 3,790/74,958 alleles
Filtering AF
4.92%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.87%
Overall
0.387%
6,237/1,611,770 alleles · common
exomes 3,672/1,459,562 · genomes 2,565/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.06% | 20 |
| Finnishnot grpmax-eligible | 0.932% | 107 |
| Remaining individualsnot grpmax-eligible | 0.75% | 133 |
| Admixed American | 0.741% | 135 |
| Middle Eastern | 0.71% | 141 |
| East Asian | 0.384% | 260 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| European (non-Finnish) | 0.0597% | 1,676 |
| South Asian | 0.0319% | 3,137 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,572 |
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
- CAPS2
- Protein
- p.Glu189=
- Coding
- c.567G>A
- MANE Select
- NM_001355024
- dbSNP
- rs35198123
- Type
- single nucleotide variant
- Location
- chr12:75304855 (GRCh38)
- Gene constraint
- LOEUF 1.457 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.30
Similar variants
- CAPS2 p.Ser52= Benign ★★ same type
- CAPS2 c.1281+1G>C Uncertain significance ★ same type
- CAPS2 c.177+130C>A Uncertain significance ★ ⚠ same type
- CAPS2 c.177+142C>T Uncertain significance ★ ⚠ same type
- CAPS2 c.177+156G>T Uncertain significance ★ ⚠ same type
- CAPS2 c.354+1G>T Uncertain significance ★ same type
- CAPS2 c.-1A>T Uncertain significance ★ ⚠ same type
- CAPS2 c.-26A>G Uncertain significance ★ ⚠ 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/caps2-p-glu189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown