CAPN5 p.Ser299=
c.897G>A · rs545510595 · VCV1583595
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.67 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -3.2 |
| Overall | ||
| CADD | 20.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.0023%
37/1,611,944 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| African / African-American | 0.004% | 25,007 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,207 |
| European (non-Finnish) | 0.00246% | 40,661 |
| Admixed American | 0.00167% | 59,780 |
| South Asian | 0.00111% | 90,332 |
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
- CAPN5
- Protein
- p.Ser299=
- Coding
- c.897G>A
- MANE Select
- NM_004055
- dbSNP
- rs545510595
- Type
- single nucleotide variant
- Location
- chr11:77116229 (GRCh38)
- Gene constraint
- LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.71 · 1 PDB
- Residue 299
- the calpain catalytic domain
Similar variants
- CAPN5 p.Ser299Leu Uncertain significance ★ ⚠ same residue
- CAPN5 p.Arg243Leu Pathogenic ★★ same type
- CAPN5 p.Arg289Trp Pathogenic ★★ ⚠ same type
- CAPN5 p.Ala118Val Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala185Val Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala245Val 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/capn5-p-ser299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown