Is SGCA p.Glu104= (c.312G>A) pathogenic?

SGCA p.Glu104= (c.312G>A) is classified Uncertain significance in SGCA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-08). Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Glu104= (c.312G>A)?

SGCA p.Glu104= (c.312G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Glu104= (c.312G>A) in the general population?

SGCA p.Glu104= (c.312G>A) is absent from gnomAD v4.1 (gnomAD).

SGCA p.Glu104=

Q: How is Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 inherited?

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

c.312G>A · rs886044401 · VCV290254

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.89	donor loss · deltas
Pangolin	Δ0.75	loss · gain 0.33 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SGCA
Protein: p.Glu104=
Coding: c.312G>A
MANE Select: NM_000023
dbSNP: rs886044401
Type: single nucleotide variant
Location: chr17:50167736 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15

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

Disease context

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

For Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

SGCA p.Glu104Lys Uncertain significance ★★ ⚠ same residue
SGCA c.37+6T>C Pathogenic ★★★ same condition
SGCA c.585-1G>A Pathogenic ★★★ same condition
SGCA c.957-11C>G Likely pathogenic ★★★ same condition
SGCA p.Ala107Val Likely pathogenic ★★★ ⚠ same condition
SGCA p.Arg192Ter Pathogenic ★★★ same condition
SGCA p.Arg221Cys Likely pathogenic ★★★ same condition
SGCA p.Arg221Pro 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/sgca-p-glu104 (accessed [today's date]).

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