Is CAPN3 p.Glu285fs (c.853dup) pathogenic?

CAPN3 p.Glu285fs (c.853dup) is classified Pathogenic/Likely pathogenic in CAPN3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-28). Ultra-rare (gnomAD MAF 6.707e-06); Associated with muscular dystrophy, limb-girdle, autosomal dominant 4.

What condition is associated with CAPN3 p.Glu285fs (c.853dup)?

CAPN3 p.Glu285fs (c.853dup) is associated with muscular dystrophy, limb-girdle, autosomal dominant 4, autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Glu285fs (c.853dup) in the general population?

CAPN3 p.Glu285fs (c.853dup) is ultra-rare (gnomAD MAF 6.707e-06) (gnomAD).

CAPN3 p.Glu285fs

Q: How is Calpain-3-related limb-girdle muscular dystrophy D4 inherited?

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

c.853dup · rs761257703 · VCV290732

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 6.707e-06)

Conditions

muscular dystrophy, limb-girdle, autosomal dominant 4

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 6 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000671% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: CAPN3
Protein: p.Glu285fs
Coding: c.853dup
MANE Select: NM_000070
dbSNP: rs761257703
Type: Duplication
Location: chr15:42389999 (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 285: the calpain catalytic domain

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

Disease context

muscular dystrophy, limb-girdle, autosomal dominant 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2A

For Calpain-3-related limb-girdle muscular dystrophy D4 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CAPN3 p.Glu285Ter Pathogenic ★★ same residue
CAPN3 p.Arg110fs Pathogenic ★★★ same condition
CAPN3 p.Asn760fs Pathogenic ★★★ same condition
CAPN3 p.Leu87fs Pathogenic ★★★ same condition
CAPN3 p.Tyr75fs Pathogenic ★★★ same condition
CAPN3 c.2115+1_2115+2dup Likely pathogenic ★★ same condition
CAPN3 p.Arg289fs Pathogenic ★★ same condition
CAPN3 p.Asn296delinsArgTer 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-glu285fs (accessed [today's date]).

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