Is SGCA p.Thr176= (c.528C>T) pathogenic?

SGCA p.Thr176= (c.528C>T) is classified Benign in SGCA (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.87%, afr); Associated with sarcoglycanopathy.

What condition is associated with SGCA p.Thr176= (c.528C>T)?

SGCA p.Thr176= (c.528C>T) is associated with sarcoglycanopathy, autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Thr176= (c.528C>T) in the general population?

SGCA p.Thr176= (c.528C>T) is low-frequency (popmax 2.87%, afr) (gnomAD).

SGCA p.Thr176=

c.528C>T · rs1801190 · VCV130293

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.87%, afr)

Conditions

sarcoglycanopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.68	GERP -2.1, phastCons 0.017
Overall
CADD	7.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.87% African / African-American · 2,138/74,460 alleles

Filtering AF 2.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.73%

Overall 0.204% 3,223/1,580,106 alleles · low-frequency exomes 1,909/1,427,836 · genomes 1,314/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.87%	35
East Asian	0.8%	125
Middle Eastern	0.414%	241
Remaining individualsnot grpmax-eligible	0.382%	262
Admixed American	0.256%	391
South Asian	0.0429%	2,333
European (non-Finnish)	0.0259%	3,862
Finnishnot grpmax-eligible	0.00162%	61,646

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.Thr176=
Coding: c.528C>T
MANE Select: NM_000023
dbSNP: rs1801190
Type: single nucleotide variant
Location: chr17:50168516 (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

sarcoglycanopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

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
SGCA p.Arg284Cys 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-thr176 (accessed [today's date]).

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