Is CAPN3 p.Asp780fs (c.2340_2341del) pathogenic?

CAPN3 p.Asp780fs (c.23402341del) is classified Likely pathogenic in CAPN3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-25). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

How common is CAPN3 p.Asp780fs (c.2340_2341del) in the general population?

CAPN3 p.Asp780fs (c.2340_2341del) is absent from gnomAD (gnomAD).

CAPN3 p.Asp780fs

Q: What condition is associated with CAPN3 p.Asp780fs (c.2340_2341del)?

CAPN3 p.Asp780fs (c.2340_2341del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A, muscular dystrophy, limb-girdle, autosomal dominant 4 (ClinVar).

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.2340_2341del · rs2548294503 · VCV2680391

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 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 22 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.9, 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.Asp780fs
Coding: c.2340_2341del
MANE Select: NM_000070
dbSNP: rs2548294503
Type: Deletion
Location: chr15:42410959 (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 780: the 'domain iv' region; an α-helix

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.Asp780His Pathogenic ★★ same residue
CAPN3 p.Asp780Ter Pathogenic/Likely pathogenic ★★ same residue
CAPN3 p.Asp780= 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-asp780fs (accessed [today's date]).

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