Is SGCA p.Ala57fs (c.168del) pathogenic?

SGCA p.Ala57fs (c.168del) is classified Pathogenic in SGCA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-08). Very rare (popmax 0.00333%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2D.

What condition is associated with SGCA p.Ala57fs (c.168del)?

SGCA p.Ala57fs (c.168del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Ala57fs (c.168del) in the general population?

SGCA p.Ala57fs (c.168del) is very rare (popmax 0.00333%, amr) (gnomAD).

SGCA p.Ala57fs

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.168del · rs1555568264 · VCV497173

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.26	GERP -2.5
Overall
CADD	18.36	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,980 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,146 alleles · very rare exomes 0/1,461,200 · genomes 2/151,946 · 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.Ala57fs
Coding: c.168del
MANE Select: NM_000023
dbSNP: rs1555568264
Type: Deletion
Location: chr17:50167590 (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.Ala57Thr Uncertain significance ★★ ⚠ same residue
SGCA p.Ala57= Likely benign ★ same residue
SGCA p.Asp385fs Uncertain significance ★★★ same condition
SGCA c.586delG Pathogenic/Likely pathogenic ★★ same condition
SGCA c.956+2_956+19del Likely pathogenic ★★ same condition
SGCA p.Asp266fs Pathogenic/Likely pathogenic ★★ same condition
SGCA p.Gly68fs Pathogenic/Likely pathogenic ★★ same condition
SGCA p.Leu131fs Pathogenic/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-ala57fs (accessed [today's date]).

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