Is CAPN3 p.Asp310= (c.930T>C) pathogenic?

CAPN3 p.Asp310= (c.930T>C) is classified Conflicting classifications of pathogenicity in CAPN3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.872%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Asp310= (c.930T>C)?

CAPN3 p.Asp310= (c.930T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Asp310= (c.930T>C) in the general population?

CAPN3 p.Asp310= (c.930T>C) is rare (popmax 0.872%, afr) (gnomAD).

CAPN3 p.Asp310=

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.930T>C · rs150356488 · VCV281357

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.872%, afr)

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.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.76	GERP -0.96, phastCons 0.022
Overall
CADD	5.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.872% African / African-American · 654/75,034 alleles

Filtering AF 0.816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.794%

Overall 0.0447% 722/1,614,150 alleles · rare exomes 359/1,461,876 · genomes 363/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.872%	115
Admixed American	0.065%	1,539
Remaining individualsnot grpmax-eligible	0.0448%	2,232
European (non-Finnish)	8.47e-05%	1,180,026

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.Asp310=
Coding: c.930T>C
MANE Select: NM_000070
dbSNP: rs150356488
Type: single nucleotide variant
Location: chr15:42390081 (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 310: the calpain catalytic 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.Asp310Asn Uncertain significance ★ ⚠ same residue
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

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-asp310 (accessed [today's date]).

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