Is SGCA p.Asp283= (c.849C>T) pathogenic?

SGCA p.Asp283= (c.849C>T) is classified Likely benign in SGCA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). Very rare (popmax 0.00446%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Asp283= (c.849C>T)?

SGCA p.Asp283= (c.849C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Asp283= (c.849C>T) in the general population?

SGCA p.Asp283= (c.849C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

SGCA p.Asp283=

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.849C>T · rs764545490 · VCV1161074

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.042	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.83	GERP -1.5, phastCons 0.081
Overall
CADD	9.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,614,226 alleles · very rare exomes 3/1,461,882 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
European (non-Finnish)	8.47e-05%	1,180,032

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: SGCA
Protein: p.Asp283=
Coding: c.849C>T
MANE Select: NM_000023
dbSNP: rs764545490
Type: single nucleotide variant
Location: chr17:50170244 (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.Asp283His Uncertain significance ★★ ⚠ same residue
SGCA p.Asp283fs Likely pathogenic 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

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-asp283 (accessed [today's date]).

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