CAPN8 p.Lys440=
c.1320G>A · rs552094413 · VCV2639919
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.919%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -2.1, phastCons 0.9 |
| Overall | ||
| CADD | 9.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.919%
African / African-American · 594/64,618 alleles
Filtering AF
0.858%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.834%
Overall
0.0531%
655/1,234,276 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.919% | 109 |
| Admixed American | 0.131% | 765 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,839 |
| South Asian | 0.0041% | 24,410 |
| East Asian | 0.00315% | 31,698 |
| European (non-Finnish) | 0.000304% | 329,368 |
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
- CAPN8
- Protein
- p.Lys440=
- Coding
- c.1320G>A
- MANE Select
- NM_001143962
- dbSNP
- rs552094413
- Type
- single nucleotide variant
- Location
- chr1:223612249 (GRCh38)
- Gene constraint
- LOEUF 1.184 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.15 · 1 PDB
Similar variants
- CAPN8 p.Ala112Val Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala136Glu Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala136Thr Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala194Ser Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala231Ser Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala234Val Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala247Val Uncertain significance ★ ⚠ same type
- CAPN8 p.Ala248Ser 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/capn8-p-lys440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown