Is CAPN3 p.Arg548fs (c.1642del) pathogenic?

CAPN3 p.Arg548fs (c.1642del) is classified Pathogenic/Likely pathogenic in CAPN3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-03). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Arg548fs (c.1642del)?

CAPN3 p.Arg548fs (c.1642del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A, muscular dystrophy, limb-girdle, autosomal dominant 4 (ClinVar).

How common is CAPN3 p.Arg548fs (c.1642del) in the general population?

CAPN3 p.Arg548fs (c.1642del) is absent from gnomAD (gnomAD).

CAPN3 p.Arg548fs

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.1642del · rs1555422293 · VCV558200

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 13 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 2.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

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.Arg548fs
Coding: c.1642del
MANE Select: NM_000070
dbSNP: rs1555422293
Type: Deletion
Location: chr15:42402898 (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 548: the 'domain iii' region

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

Also linked: muscular dystrophy, limb-girdle, autosomal dominant 4

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.Arg548Cys Uncertain significance ★★ ⚠ same residue
CAPN3 p.Arg548His Conflicting classifications of pathogenicity ★ ⚠ same residue
CAPN3 p.Arg548= Likely benign ★ 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

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-arg548fs (accessed [today's date]).

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