Is SGCD p.Ala239= (c.717G>A) pathogenic?

SGCD p.Ala239= (c.717G>A) is classified Conflicting classifications of pathogenicity in SGCD (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-30). Very rare (popmax 0.00891%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2F.

What condition is associated with SGCD p.Ala239= (c.717G>A)?

SGCD p.Ala239= (c.717G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2F, qualitative or quantitative defects of delta-sarcoglycan (ClinVar).

How common is SGCD p.Ala239= (c.717G>A) in the general population?

SGCD p.Ala239= (c.717G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

SGCD p.Ala239=

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.717G>A · rs145430692 · VCV378577

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2F

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	acceptor loss, 17 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.58	GERP -3.7, phastCons 0.99
Overall
CADD	10.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.00638% 103/1,613,654 alleles · very rare exomes 88/1,461,428 · genomes 15/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,219
European (non-Finnish)	0.00797%	12,550
Remaining individualsnot grpmax-eligible	0.0064%	15,618
South Asian	0.0011%	91,052

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.Ala239=
Coding: c.717G>A
MANE Select: NM_000337
dbSNP: rs145430692
Type: single nucleotide variant
Location: chr5:156759234 (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: qualitative or quantitative defects of delta-sarcoglycan

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.Ala239Val Uncertain significance ★★ ⚠ same residue
SGCD p.Ala239Thr 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-ala239 (accessed [today's date]).

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