Is CAPN3 p.Ile47del (c.137TCA[1]) pathogenic?

CAPN3 p.Ile47del (c.137TCA[1]) is classified Likely pathogenic in CAPN3 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 8.47e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Ile47del (c.137TCA[1])?

CAPN3 p.Ile47del (c.137TCA[1]) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Ile47del (c.137TCA[1]) in the general population?

CAPN3 p.Ile47del (c.137TCA[1]) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CAPN3 p.Ile47del

Q: How is Calpain-3-related limb-girdle muscular dystrophy R1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.137TCA[1] · VCV3340140

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,868 alleles · very rare

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: CAPN3
Protein: p.Ile47del
Coding: c.137TCA[1]
MANE Select: NM_000070
Type: Microsatellite
Location: chr15:42359940 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.18 · 5 PDB

Full CAPN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Calpain-3-related limb-girdle muscular dystrophy R1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CAPN3 p.Ile47= Likely benign ★ same residue
CAPN3 p.Glu467del Pathogenic ★★★ same condition
CAPN3 p.Lys254del Pathogenic ★★★ same condition
CAPN3 p.His690fs Pathogenic ★★ same condition
CAPN3 p.Ser581fs Pathogenic/Likely pathogenic ★★ same condition
CAPN3 p.Thr679fs Pathogenic ★★ same condition
CAPN3 p.Thr736fs Pathogenic/Likely pathogenic ★★ same condition
CAPN3 p.Val433fs 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-ile47del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown