Is SGCA p.Arg98Pro (c.293G>C) pathogenic?

SGCA p.Arg98Pro (c.293G>C) is classified Conflicting classifications of pathogenicity in SGCA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-28). AlphaMissense: ambiguous (0.3505); Very rare (popmax 0.00267%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Arg98Pro (c.293G>C)?

SGCA p.Arg98Pro (c.293G>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Arg98Pro (c.293G>C) in the general population?

SGCA p.Arg98Pro (c.293G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about SGCA p.Arg98Pro (c.293G>C)?

AlphaMissense predicts ambiguous (score 0.3505) — an in-silico prediction, not a clinical call.

SGCA p.Arg98Pro

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.293G>C · rs137852621 · VCV283227

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3505 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2D

Computational evidence

Protein change
AlphaMissense	0.3505	ambiguous
REVEL	0.395	indeterminate
SaProt	LLR -12.79	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP -2.5, phastCons 0.89
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	22.8	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 0.00267% African / African-American · 2/74,858 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,611,560 alleles · very rare exomes 2/1,459,378 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,429
European (non-Finnish)	8.49e-05%	1,178,330

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.Arg98Pro
Coding: c.293G>C
MANE Select: NM_000023
dbSNP: rs137852621
Type: single nucleotide variant
Location: chr17:50167717 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15
Residue 98: a UniProt-annotated variant site (in lgmdr3)

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.Arg98Cys Pathogenic ★★★ ⚠ same residue
SGCA p.Arg98His Pathogenic ★★★ ⚠ same residue
SGCA p.Arg98Ser Pathogenic/Likely pathogenic ★★ ⚠ same residue
SGCA p.Arg98Gly 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

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-arg98pro (accessed [today's date]).

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