Is CAPN3 p.Ser202= (c.606T>C) pathogenic?

CAPN3 p.Ser202= (c.606T>C) is classified Benign/Likely benign in CAPN3 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Ser202= (c.606T>C)?

CAPN3 p.Ser202= (c.606T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

CAPN3 p.Ser202=

Q: How common is CAPN3 p.Ser202= (c.606T>C) in the general population?

CAPN3 p.Ser202= (c.606T>C) is common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.606T>C · rs17593 · VCV128573

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -5.7
Overall
CADD	1.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.4% African / African-American · 12,283/74,980 alleles

Filtering AF 16.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 16%

Overall 1.25% 20,106/1,613,942 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.4%	6
Middle Eastern	3.25%	31
Ashkenazi Jewishnot grpmax-eligible	2.76%	36
South Asian	2.26%	44
Remaining individualsnot grpmax-eligible	1.78%	56
Admixed American	1.47%	68
European (non-Finnish)	0.232%	431
Finnishnot grpmax-eligible	0.0156%	6,400
East Asian	0.00669%	14,956

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.Ser202=
Coding: c.606T>C
MANE Select: NM_000070
dbSNP: rs17593
Type: single nucleotide variant
Location: chr15:42387860 (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 202: the calpain catalytic domain; an α-helix; a UniProt-annotated variant site (in lgmdr1)

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.Ser202Ile 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-ser202 (accessed [today's date]).

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