Is CAPN3 p.Phe604fs (c.1807_1808dup) pathogenic?

CAPN3 p.Phe604fs (c.18071808dup) is classified Likely pathogenic in CAPN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-20). Absent from gnomAD; Associated with muscular dystrophy, limb-girdle, autosomal dominant 4.

What condition is associated with CAPN3 p.Phe604fs (c.1807_1808dup)?

CAPN3 p.Phe604fs (c.1807_1808dup) is associated with muscular dystrophy, limb-girdle, autosomal dominant 4 (ClinVar).

How common is CAPN3 p.Phe604fs (c.1807_1808dup) in the general population?

CAPN3 p.Phe604fs (c.1807_1808dup) is absent from gnomAD (gnomAD).

CAPN3 p.Phe604fs

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.1807_1808dup · rs2548287742 · VCV2680379

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 16 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 2.6, 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.Phe604fs
Coding: c.1807_1808dup
MANE Select: NM_000070
dbSNP: rs2548287742
Type: Duplication
Location: chr15:42408216 (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 604: the 'linker' region

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

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.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.Asn296delinsArgTer Likely pathogenic ★★ same condition
CAPN3 p.Asp780Ter Pathogenic/Likely pathogenic ★★ same condition
CAPN3 p.Gln638fs 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-phe604fs (accessed [today's date]).

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