CAPN3 p.Glu582fs
c.1743_1744del · rs886042573 · VCV283179
ClinGen expert panel — Limb Girdle Muscular Dystrophy VCEP
Pathogenic for autosomal recessive limb-girdle muscular dystrophy. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting PP4
Curation rationale (ClinGen, verbatim)
The NM_000070.3: c.1743_1744del p.(Glu582GlyfsTer3) variant in CAPN3 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 13/24, leading to nonsense-mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been identified in at least two patients with features consistent with LGMD (PMID: 30564623, 15689361, 10330340), at least one of whom had a second presumed diagnostic CAPN3 variant as well as a clinical suspicion of LGMD (PMID: 15689361, LOVD Individual #00214348; PP4). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb-girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Limb Girdle Muscular Dystrophy Expert Panel (specifications version 2.0.0; 02/18/2026): PVS1, PM2_Supporting, PP4.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 24 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 0.87, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- CAPN3
- Protein
- p.Glu582fs
- Coding
- c.1743_1744del
- MANE Select
- NM_000070
- dbSNP
- rs886042573
- Type
- Deletion
- Location
- chr15:42403000 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 79.18 · 5 PDB
- Residue 582
- the 'domain iii' region
Similar variants
- CAPN3 p.Glu582Ter Likely pathogenic ★ same residue
- CAPN3 c.1194-2del Pathogenic ★★★ same condition
- CAPN3 p.Asp764fs Pathogenic ★★★ same condition
- CAPN3 p.Gln660_Ile661insTer Pathogenic ★★★ same condition
- CAPN3 p.Gly441fs Pathogenic ★★★ same condition
- CAPN3 p.Leu74fs Likely pathogenic ★★★ same condition
- CAPN3 p.Lys613fs Pathogenic ★★★ same condition
- CAPN3 p.Phe200_Leu204del Pathogenic ★★★ same condition
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/capn3-p-glu582fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown