SGCD

Chr 5AR

sarcoglycan delta

Also known as: 35DAG, CMD1L, DAGD, LGMDR6, SG-delta, SGCDP, SGD

The protein is a component of the sarcoglycan complex within the dystrophin-glycoprotein complex, linking the F-actin cytoskeleton to the extracellular matrix in skeletal and cardiac muscle. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 6 and dilated cardiomyopathy through loss of function. The inheritance pattern is autosomal recessive.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 0.822 OMIM phenotypes
VCEP Guidelines: Limb Girdle Muscular DystrophyReleased
ClinGen Panel
Clinical SummarySGCD
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Gene-Disease Validity (ClinGen)
autosomal recessive limb-girdle muscular dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 187 VUS of 500 total submissions
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GeneReview available — SGCD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.002
Z-score 2.08
OE 0.44 (0.250.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.20Z-score
OE missense 0.96 (0.831.10)
144 obs / 150.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.250.82)
00.351.4
Missense OE0.96 (0.831.10)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 7 / 15.9Missense obs/exp: 144 / 150.7Syn Z: -0.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSGCD-related dilated cardiomyopathyOTHERAD
DN
0.82top 10%
GOF
0.7029th %ile
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

500 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic20
VUS187
Likely Benign234
Benign27
Conflicting1
26
Pathogenic
20
Likely Pathogenic
187
VUS
234
Likely Benign
27
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
9
0
26
Likely Pathogenic
17
1
2
0
20
VUS
5
126
54
2
187
Likely Benign
0
8
127
99
234
Benign
3
0
24
0
27
Conflicting
1
Total42135216101495

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

View in ClinVar →

Protein Context — Lollipop Plot

SGCD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →