Is CAPN3 p.Ala203Val (c.608C>T) pathogenic?

CAPN3 p.Ala203Val (c.608C>T) is classified Conflicting classifications of pathogenicity in CAPN3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-04). AlphaMissense: likely pathogenic (0.9147); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with CAPN3 p.Ala203Val (c.608C>T)?

CAPN3 p.Ala203Val (c.608C>T) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Ala203Val (c.608C>T) in the general population?

CAPN3 p.Ala203Val (c.608C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CAPN3 p.Ala203Val (c.608C>T)?

AlphaMissense predicts likely pathogenic (score 0.9147) — an in-silico prediction, not a clinical call.

CAPN3 p.Ala203Val

c.608C>T · rs763719290 · VCV289751

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9147 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9147	likely pathogenic
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -11.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 52 kb · p 0.21 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,074 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000479% 7/1,461,834 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,769
European (non-Finnish)	0.000254%	393,328

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.Ala203Val
Coding: c.608C>T
MANE Select: NM_000070
dbSNP: rs763719290
Type: single nucleotide variant
Location: chr15:42387862 (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 203: 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

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.Ala203Gly Pathogenic ★ same residue
CAPN3 p.Ala203= Likely benign ★ 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-ala203val (accessed [today's date]).

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