Is AGA p.Ile192Val (c.574A>G) pathogenic?

AGA p.Ile192Val (c.574A>G) is classified Uncertain significance in AGA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). AlphaMissense: likely benign (0.0662); Very rare (popmax 0.008%, afr); Associated with aspartylglucosaminuria.

What condition is associated with AGA p.Ile192Val (c.574A>G)?

AGA p.Ile192Val (c.574A>G) is associated with aspartylglucosaminuria (ClinVar).

How common is AGA p.Ile192Val (c.574A>G) in the general population?

AGA p.Ile192Val (c.574A>G) is very rare (popmax 0.008%, afr) (gnomAD).

How is Aspartylglucosaminuria inherited?

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

What do computational predictors say about AGA p.Ile192Val (c.574A>G)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

AGA p.Ile192Val

c.574A>G · rs189159117 · VCV1434186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aspartylglucosaminuria

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.68	GERP -2.5
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic
Overall
CADD	0.051	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/75,044 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000372% 6/1,613,616 alleles · very rare exomes 3/1,461,264 · genomes 3/152,352 · 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: AGA
Protein: p.Ile192Val
Coding: c.574A>G
MANE Select: NM_000027
dbSNP: rs189159117
Type: single nucleotide variant
Location: chr4:177437453 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.41 · 2 PDB

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 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
AGA c.508-2A>G Likely pathogenic ★★ same condition
AGA c.698+1G>T 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/aga-p-ile192val (accessed [today's date]).

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