SGCD p.Arg97Ter
c.289C>T · rs758700138 · VCV1677453
ClinGen expert panel — Limb Girdle Muscular Dystrophy VCEP
Pathogenic for autosomal recessive limb-girdle muscular dystrophy. Applied ACMG criteria (verbatim):
PVS1 PM3_Supporting PM2_Supporting PP4
Curation rationale (ClinGen, verbatim)
The NM_000337.6: c.289C>T p.(Arg97Ter) variant in SGCD is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 4/9, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been identified in a homozygous state in at least two patients with LGMD who were from consanguineous families (0.5 pts, PMID: 34515763, 30733730; PM3_Supporting). At least one of these patients displayed progressive limb girdle weakness observed over more than six months (PP4). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00001146 (1/87260 alleles) in the South Asian population, which is lower than the ClinGen LGMD VCEP threshold (<0.00009) for PM2_Supporting, 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, PM3_Supporting, PP4, 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 4 of 9 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.15, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Arg97Ter
- Coding
- c.289C>T
- MANE Select
- NM_000337
- dbSNP
- rs758700138
- Type
- single nucleotide variant
- Location
- chr5:156508697 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 81.43
Similar variants
- SGCD p.Arg97Gln Benign/Likely benign ★★ same residue
- SGCD p.Arg97= Likely benign ★ same residue
- SGCD p.Arg165Ter 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
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-arg97ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown