CAPN1 p.Ser589=
c.1767G>A · rs78742312 · VCV727352
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.88%, 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 -9.2 | GERP -3.4 |
| Overall | ||
| CADD | 6.508 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.88%
African / African-American · 1,414/75,036 alleles
Filtering AF
1.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.77%
Overall
0.12%
1,931/1,613,796 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.88% | 53 |
| Remaining individualsnot grpmax-eligible | 0.17% | 589 |
| Admixed American | 0.157% | 638 |
| Middle Eastern | 0.033% | 3,030 |
| European (non-Finnish) | 0.0255% | 3,920 |
| South Asian | 0.0121% | 8,278 |
| East Asian | 0.00668% | 14,960 |
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
- CAPN1
- Protein
- p.Ser589=
- Coding
- c.1767G>A
- MANE Select
- NM_005186
- dbSNP
- rs78742312
- Type
- single nucleotide variant
- Location
- chr11:65209360 (GRCh38)
- Gene constraint
- LOEUF 0.977 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.03 · 5 PDB
- Residue 589
- the ef-hand 2 domain; the 'domain iv' region
Similar variants
- CAPN1 p.Ser589Leu Uncertain significance ★★ ⚠ same residue
- CAPN1 c.1605+5G>A Pathogenic/Likely pathogenic ★★ same type
- CAPN1 c.267+2T>C Pathogenic/Likely pathogenic ★★ same type
- CAPN1 c.338-1G>A Pathogenic ★★ same type
- CAPN1 c.759+1G>A Pathogenic ★★ same type
- CAPN1 c.843+1G>C Pathogenic/Likely pathogenic ★★ same type
- CAPN1 c.929+2T>A Likely pathogenic ★★ same type
- CAPN1 p.Arg285Ter 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/capn1-p-ser589 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown