Is CAPN3 p.Asp267= (c.801T>C) pathogenic?

CAPN3 p.Asp267= (c.801T>C) is classified Uncertain significance in CAPN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). Very rare (popmax 0.00178%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2A.

What condition is associated with CAPN3 p.Asp267= (c.801T>C)?

CAPN3 p.Asp267= (c.801T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Asp267= (c.801T>C) in the general population?

CAPN3 p.Asp267= (c.801T>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

CAPN3 p.Asp267=

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.801T>C · rs1271482252 · VCV1037134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

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 -0.46	GERP -0.59, phastCons 0.17
Overall
CADD	12.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,934 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00149% 24/1,613,718 alleles · very rare exomes 23/1,461,756 · genomes 1/151,962 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)grpmax	0.00178%	56,187
Admixed American	0.00167%	59,982

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp267=
Coding: c.801T>C
MANE Select: NM_000070
dbSNP: rs1271482252
Type: single nucleotide variant
Location: chr15:42389096 (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 267: the calpain catalytic domain; 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 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-asp267 (accessed [today's date]).

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