SGCD p.Arg165Ter
c.493C>T · rs121909295 · VCV8172
ClinGen expert panel — Limb Girdle Muscular Dystrophy VCEP
Pathogenic for autosomal recessive limb-girdle muscular dystrophy. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting PP4_Strong PM3
Curation rationale (ClinGen, verbatim)
The NM_000337.6: c.493C>T p.(Arg165Ter) variant in SGCD is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 6/9, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been detected in at least three patients with limb girdle muscular dystrophy, including in homozygous state in at least two patients from two families (1.0 pt, PMID: 19770540, 10735275) (PM3). At least one patient with this variant displayed progressive limb girdle muscle weakness as well as absent delta-sarcoglycan protein expression in skeletal muscle by IHC, which is highly specific for SGCD-related LGMD (PP4_Strong; PMID: 19770540). The highest population minor allele frequency for this variant is 0.00004827 (2/41432 genome chromosomes) in the African/African American population of gnomAD v3.1.2, which is lower than the ClinGen LGMD VCEP threshold for PM2_Supporting (<0.00009), meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): PVS1, PP4_Strong, PM3, PM2_Supporting.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 9 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -3.5, phastCons 0.95 |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,476 |
| Finnishnot grpmax-eligible | 0.00156% | 63,912 |
| European (non-Finnish) | 0.000679% | 147,283 |
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
- SGCD
- Protein
- p.Arg165Ter
- Coding
- c.493C>T
- MANE Select
- NM_000337
- dbSNP
- rs121909295
- Type
- single nucleotide variant
- Location
- chr5:156595042 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 81.43
Similar variants
- SGCD p.Arg165Gln Uncertain significance ★★ ⚠ same residue
- SGCD p.Arg97Ter Pathogenic ★★★ same condition
- SGCD p.Arg31Gly Uncertain significance ★★★ ⚠ same condition
- SGCD p.Arg31Trp Uncertain significance ★★★ ⚠ same condition
- SGCD p.Ile64Thr Uncertain significance ★★★ ⚠ same condition
- SGCD c.192+1G>A Likely pathogenic ★★ same condition
- SGCD c.294+1G>A Likely pathogenic ★★ same condition
- SGCD c.4-1G>T Likely 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/sgcd-p-arg165ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown