Is CAPN3 p.Asp707fs (c.2118_2121del) pathogenic?

CAPN3 p.Asp707fs (c.21182121del) is classified Pathogenic in CAPN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Very rare (popmax 8.47e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Asp707fs (c.2118_2121del)?

CAPN3 p.Asp707fs (c.2118_2121del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Asp707fs (c.2118_2121del) in the general population?

CAPN3 p.Asp707fs (c.2118_2121del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CAPN3 p.Asp707fs

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.2118_2121del · rs1595846922 · VCV659272

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 20 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,946 alleles

Overall 6.84e-05% 1/1,461,784 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.Asp707fs
Coding: c.2118_2121del
MANE Select: NM_000070
dbSNP: rs1595846922
Type: Deletion
Location: chr15:42410430 (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 707: the 'domain iv' region; a binding site; the ef-hand 2 domain

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.Asp707Gly Pathogenic ★★★ same residue
CAPN3 p.Asp707His Conflicting classifications of pathogenicity ★ ⚠ same residue
CAPN3 c.1194-2del Pathogenic ★★★ same condition
CAPN3 p.Asp764fs Pathogenic ★★★ same condition
CAPN3 p.Gln660_Ile661insTer Pathogenic ★★★ same condition
CAPN3 p.Glu582fs Pathogenic ★★★ same condition
CAPN3 p.Gly441fs Pathogenic ★★★ same condition
CAPN3 p.Leu74fs Likely 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-asp707fs (accessed [today's date]).

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