SGCA

Chr 17AR

sarcoglycan alpha

Also known as: 50DAG, ADL, DAG2, DMDA2, LGMD2D, LGMDR3, SCARMD1, adhalin

NCBI Gene: 6442 ENSG00000108823 UniProt: Q16586 OMIM: 600119

This protein is a component of the dystrophin-glycoprotein complex that stabilizes muscle fiber membranes and links the actin cytoskeleton to the extracellular matrix in striated muscle. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 2D through a predicted gain-of-function mechanism. The inheritance pattern is autosomal recessive.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 0.791 OMIM phenotype

VCEP Guidelines: Limb Girdle Muscular DystrophyReleased

ClinGen Panel

Clinical Summary— SGCA

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Gene-Disease Validity (ClinGen)

autosomal recessive limb-girdle muscular dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

203 unique Pathogenic / Likely Pathogenic· 234 VUS of 855 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SGCA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.003

Z-score 2.19

OE 0.42 (0.24–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.68Z-score

OE missense 0.88 (0.79–0.98)

214 obs / 243.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.24–0.79)

0≤0.351.4

Missense OE?0.88 (0.79–0.98)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 7 / 16.7Missense obs/exp: 214 / 243.7Syn Z: 0.11

This gene — mechanism propensity

0.6064th %ile

GOF

0.6638th %ile

LOF

0.3068th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

855 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64

Likely Pathogenic139

VUS234

Likely Benign323

Benign31

Conflicting62

Pathogenic

139

Likely Pathogenic

234

VUS

323

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	42	15	7	0	64
Likely Pathogenic	83	50	5	1	139
VUS	3	198	22	11	234
Likely Benign	0	1	134	188	323
Benign	0	1	28	2	31
Conflicting	—				62
Total	128	265	196	202	853

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap SGCA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →