Is CAPN3 p.Asp175= (c.525C>T) pathogenic?

CAPN3 p.Asp175= (c.525C>T) is classified Conflicting classifications of pathogenicity in CAPN3 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-31). Rare (popmax 0.12%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Asp175= (c.525C>T)?

CAPN3 p.Asp175= (c.525C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Asp175= (c.525C>T) in the general population?

CAPN3 p.Asp175= (c.525C>T) is rare (popmax 0.12%, nfe) (gnomAD).

CAPN3 p.Asp175=

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.525C>T · rs144383442 · VCV197103

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor loss, 26 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -7.3	GERP -5.7
Overall
CADD	5.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% European (non-Finnish) · 1,420/1,180,022 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.0955% 1,541/1,614,144 alleles · rare exomes 1,446/1,461,870 · genomes 95/152,274 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.12%	831
South Asian	0.0527%	1,897
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Finnishnot grpmax-eligible	0.0406%	2,463
African / African-American	0.0147%	6,820
Admixed American	0.0133%	7,502
East Asian	0.00223%	44,888

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CAPN3
Protein: p.Asp175=
Coding: c.525C>T
MANE Select: NM_000070
dbSNP: rs144383442
Type: single nucleotide variant
Location: chr15:42387779 (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 175: the calpain catalytic domain; a β-strand

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 c.1115+5G>C Pathogenic ★★★ same condition
CAPN3 c.1194-2A>G Pathogenic ★★★ same condition
CAPN3 c.1194-9A>G Pathogenic ★★★ same condition
CAPN3 c.1746-20C>G Pathogenic ★★★ same condition
CAPN3 c.1993-1G>A Pathogenic ★★★ same condition
CAPN3 c.499-1G>A Pathogenic ★★★ same condition
CAPN3 p.Ala702Val Pathogenic ★★★ same condition
CAPN3 p.Ala798Glu 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-asp175 (accessed [today's date]).

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