Is SGCA p.Arg98Ser (c.292C>A) pathogenic?

SGCA p.Arg98Ser (c.292C>A) is classified Pathogenic/Likely pathogenic in SGCA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). AlphaMissense: likely benign (0.2407); Very rare (popmax 0.000255%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy.

What condition is associated with SGCA p.Arg98Ser (c.292C>A)?

SGCA p.Arg98Ser (c.292C>A) is associated with autosomal recessive limb-girdle muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Arg98Ser (c.292C>A) in the general population?

SGCA p.Arg98Ser (c.292C>A) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about SGCA p.Arg98Ser (c.292C>A)?

AlphaMissense predicts likely benign (score 0.2407) — an in-silico prediction, not a clinical call.

SGCA p.Arg98Ser

c.292C>A · VCV3384982

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2407 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2407	likely benign ⚠ discordant with ClinVar
REVEL	0.561	indeterminate
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP 0.14, phastCons 0.49
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	26.5	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 0.000255% European (non-Finnish) · 3/1,178,462 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,858 alleles · very rare exomes 3/1,459,560 · genomes 0/152,298 · joint denominator

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.Arg98Ser
Coding: c.292C>A
MANE Select: NM_000023
Type: single nucleotide variant
Location: chr17:50167716 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2D

Similar variants

SGCA p.Arg98Cys Pathogenic ★★★ ⚠ same residue
SGCA p.Arg98His Pathogenic ★★★ ⚠ same residue
SGCA p.Arg98Gly Pathogenic ★ ⚠ same residue
SGCA p.Arg98Pro Conflicting classifications of pathogenicity ★ 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-arg98ser (accessed [today's date]).

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