Is CAPN3 p.Thr32= (c.96T>C) pathogenic?

CAPN3 p.Thr32= (c.96T>C) is classified Benign/Likely benign in CAPN3 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Common (popmax 19.6%, sas) — too common for a highly-penetrant pathogenic allele; Associated with myopathy, centronuclear, 2.

How is Autosomal recessive centronuclear myopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CAPN3 p.Thr32=

Q: What condition is associated with CAPN3 p.Thr32= (c.96T>C)?

CAPN3 p.Thr32= (c.96T>C) is associated with myopathy, centronuclear, 2, autosomal recessive limb-girdle muscular dystrophy type 2A, muscular dystrophy, limb-girdle, autosomal dominant 4 (ClinVar).

Q: How common is CAPN3 p.Thr32= (c.96T>C) in the general population?

CAPN3 p.Thr32= (c.96T>C) is common (popmax 19.6%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.96T>C · rs1801496 · VCV92422

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Common

common (popmax 19.6%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

myopathy, centronuclear, 2

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 -11	GERP -5.3
Overall
CADD	0.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.6% South Asian · 17,893/91,086 alleles

Filtering AF 19.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.3%

Overall 8.72% 140,821/1,614,140 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	19.6%	5
Middle Eastern	13.9%	7
African / African-American	13.3%	8
Ashkenazi Jewishnot grpmax-eligible	12.6%	8
Finnishnot grpmax-eligible	10.1%	10
Remaining individualsnot grpmax-eligible	9.36%	11
European (non-Finnish)	7.86%	13
Admixed American	5.47%	18
Amishnot grpmax-eligible	0.219%	456
East Asian	0.165%	607

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.Thr32=
Coding: c.96T>C
MANE Select: NM_000070
dbSNP: rs1801496
Type: single nucleotide variant
Location: chr15:42359901 (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 32: the 'disordered' region

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

Disease context

myopathy, centronuclear, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2A muscular dystrophy, limb-girdle, autosomal dominant 4

For Autosomal recessive centronuclear myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

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-thr32 (accessed [today's date]).

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