Is AGA p.Cys179= (c.537C>T) pathogenic?

AGA p.Cys179= (c.537C>T) is classified Likely benign in AGA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0824%, mid); Associated with aspartylglucosaminuria.

What condition is associated with AGA p.Cys179= (c.537C>T)?

AGA p.Cys179= (c.537C>T) is associated with aspartylglucosaminuria (ClinVar).

How common is AGA p.Cys179= (c.537C>T) in the general population?

AGA p.Cys179= (c.537C>T) is ultra-rare (popmax 0.0824%, mid) (gnomAD).

How is Aspartylglucosaminuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGA p.Cys179=

c.537C>T · rs748171793 · VCV1118434

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, mid)

Conditions

aspartylglucosaminuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.097	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.47, phastCons 1
Overall
CADD	12.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0824% Middle Eastern · 5/6,070 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00571% 92/1,611,434 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0824%	1,214
European (non-Finnish)	0.00654%	15,296
African / African-American	0.00534%	18,714
Remaining individualsnot grpmax-eligible	0.00481%	20,800
East Asian	0.00223%	44,792
Admixed American	0.00167%	59,986
South Asian	0.0011%	91,042

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: AGA
Protein: p.Cys179=
Coding: c.537C>T
MANE Select: NM_000027
dbSNP: rs748171793
Type: single nucleotide variant
Location: chr4:177437490 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.41 · 2 PDB
Residue 179: a disulfide bond

Full AGA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Aspartylglucosaminuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Australia)

Similar variants

AGA p.Cys179Ter Pathogenic ★ same residue
AGA p.Cys179Arg Uncertain significance ★ ⚠ same residue
AGA c.127+1G>A Likely pathogenic ★★ same condition
AGA c.127+1G>T Likely pathogenic ★★ same condition
AGA c.128-2A>G Pathogenic ★★ same condition
AGA c.281+1G>T Likely pathogenic ★★ same condition
AGA c.395-8A>G Pathogenic/Likely pathogenic ★★ same condition
AGA c.508-2A>C 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/aga-p-cys179 (accessed [today's date]).

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