Is CAPN3 p.Pro82= (c.246G>A) pathogenic?

CAPN3 p.Pro82= (c.246G>A) is classified Likely benign in CAPN3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-25). Rare (popmax 0.127%, afr); Associated with Inborn genetic diseases.

What condition is associated with CAPN3 p.Pro82= (c.246G>A)?

CAPN3 p.Pro82= (c.246G>A) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Pro82= (c.246G>A) in the general population?

CAPN3 p.Pro82= (c.246G>A) is rare (popmax 0.127%, afr) (gnomAD).

CAPN3 p.Pro82=

c.246G>A · rs146529432 · VCV254870

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.127%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.3	GERP -5.3
Overall
CADD	6.511	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.127% African / African-American · 95/75,048 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0982%

Overall 0.00805% 130/1,614,192 alleles · rare exomes 79/1,461,860 · genomes 51/152,332 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.127%	790
Admixed American	0.0133%	7,504
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00446%	22,445
South Asian	0.00329%	30,363
European (non-Finnish)	0.00144%	69,413

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.Pro82=
Coding: c.246G>A
MANE Select: NM_000070
dbSNP: rs146529432
Type: single nucleotide variant
Location: chr15:42360051 (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 82: the calpain catalytic domain

Full CAPN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2A

Similar variants

CAPN3 p.Pro82Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CAPN3 p.Pro82fs Pathogenic ★ 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

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-pro82 (accessed [today's date]).

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