Is CAPN3 p.Thr679fs (c.2036_2037del) pathogenic?

CAPN3 p.Thr679fs (c.20362037del) is classified Pathogenic in CAPN3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-20). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Thr679fs (c.2036_2037del)?

CAPN3 p.Thr679fs (c.2036_2037del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Thr679fs (c.2036_2037del) in the general population?

CAPN3 p.Thr679fs (c.2036_2037del) is absent from gnomAD (gnomAD).

CAPN3 p.Thr679fs

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.2036_2037del · rs886042418 · VCV282536

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 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 18 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	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.Thr679fs
Coding: c.2036_2037del
MANE Select: NM_000070
dbSNP: rs886042418
Type: Microsatellite
Location: chr15:42409827 (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 679: the 'domain iv' region; an α-helix; the ef-hand 1 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.Thr679= Likely benign ★★ same residue
CAPN3 p.Glu467del Pathogenic ★★★ same condition
CAPN3 p.Lys254del Pathogenic ★★★ same condition
CAPN3 p.His690fs Pathogenic ★★ same condition
CAPN3 p.Ser581fs Pathogenic/Likely pathogenic ★★ same condition
CAPN3 p.Thr736fs Pathogenic/Likely pathogenic ★★ same condition
CAPN3 p.Val433fs Pathogenic ★★ same condition
CAPN3 c.2440-10CTT[3] Benign/Likely benign ★★ 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-thr679fs (accessed [today's date]).

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