Is SGCD p.Cys221Ter (c.663C>A) pathogenic?

SGCD p.Cys221Ter (c.663C>A) is classified Uncertain significance in SGCD (ClinVar, Single submitter, 2 submitters; last evaluated 2020-06-10). No allele count reported in gnomAD v4.1 (AN 1,608,718); Associated with autosomal recessive limb-girdle muscular dystrophy type 2F.

How common is SGCD p.Cys221Ter (c.663C>A) in the general population?

SGCD p.Cys221Ter (c.663C>A) is no allele count reported in gnomAD v4.1 (AN 1,608,718) (gnomAD).

SGCD p.Cys221Ter

Q: What condition is associated with SGCD p.Cys221Ter (c.663C>A)?

SGCD p.Cys221Ter (c.663C>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2F, dilated cardiomyopathy 1L (ClinVar).

Q: How is Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.663C>A · rs1175344271 · VCV557026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,718)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2F

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 36 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.8, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,608,718). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SGCD
Protein: p.Cys221Ter
Coding: c.663C>A
MANE Select: NM_000337
dbSNP: rs1175344271
Type: single nucleotide variant
Location: chr5:156757668 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 81.43

Full SGCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1L

For Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

SGCD p.Cys221Tyr Uncertain significance ★ ⚠ same residue
SGCD p.Cys221Ser Uncertain significance ★ ⚠ same residue
SGCD p.Arg165Ter Pathogenic ★★★ same condition
SGCD p.Arg97Ter Pathogenic ★★★ 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-cys221ter (accessed [today's date]).

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