Is SGCA p.Asp328Val (c.983A>T) pathogenic?

SGCA p.Asp328Val (c.983A>T) is classified Uncertain significance in SGCA (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.5454); Ultra-rare (popmax 0.0204%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Asp328Val (c.983A>T)?

SGCA p.Asp328Val (c.983A>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Asp328Val (c.983A>T) in the general population?

SGCA p.Asp328Val (c.983A>T) is ultra-rare (popmax 0.0204%, afr) (gnomAD).

What do computational predictors say about SGCA p.Asp328Val (c.983A>T)?

AlphaMissense predicts ambiguous (score 0.5454) — an in-silico prediction, not a clinical call.

SGCA p.Asp328Val

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.983A>T · rs966135192 · VCV641422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5454 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2D

Computational evidence

Protein change
AlphaMissense	0.5454	ambiguous
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -6.66	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% African / African-American · 15/73,536 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.0016% 25/1,559,612 alleles · ultra-rare exomes 12/1,407,452 · genomes 13/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0204%	4,902
Remaining individualsnot grpmax-eligible	0.00497%	20,134
European (non-Finnish)	0.000608%	164,380

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.Asp328Val
Coding: c.983A>T
MANE Select: NM_000023
dbSNP: rs966135192
Type: single nucleotide variant
Location: chr17:50170666 (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.Asp328fs 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
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-asp328val (accessed [today's date]).

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