Is AGXT p.Cys173Arg (c.517T>C) pathogenic?

AGXT p.Cys173Arg (c.517T>C) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-12). AlphaMissense: likely pathogenic (0.9579); Absent from gnomAD v4.1; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Cys173Arg (c.517T>C)?

AGXT p.Cys173Arg (c.517T>C) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Cys173Arg (c.517T>C) in the general population?

AGXT p.Cys173Arg (c.517T>C) is absent from gnomAD v4.1 (gnomAD).

How is Primary hyperoxaluria inherited?

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

What do computational predictors say about AGXT p.Cys173Arg (c.517T>C)?

AlphaMissense predicts likely pathogenic (score 0.9579) — an in-silico prediction, not a clinical call.

AGXT p.Cys173Arg

c.517T>C · rs2106428650 · VCV2675194

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9579 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,587,392)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.9579	likely pathogenic · top 1% in AGXT
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -15.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	27.2	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

No allele count reported in gnomAD v4.1 (AN 1,587,392). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGXT
Protein: p.Cys173Arg
Coding: c.517T>C
MANE Select: NM_000030
dbSNP: rs2106428650
Type: single nucleotide variant
Location: chr2:240871442 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB
Residue 173: a UniProt-annotated variant site (in hp1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; decreased protein stability; causes protein aggregation); an α-helix

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

Disease context

primary hyperoxaluria type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary hyperoxaluria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Germany)

Similar variants

AGXT p.Cys173Ter Pathogenic ★ same residue
AGXT p.Cys173Tyr Likely pathogenic ★ same residue
AGXT p.Cys173_His174delinsTrpAsn Pathogenic/Likely pathogenic ★★ same residue
AGXT p.Cys173= Likely benign ★ same residue
AGXT c.358+1G>A Pathogenic ★★ same condition
AGXT c.359-2A>G Likely pathogenic ★★ same condition
AGXT c.423+1G>A Pathogenic/Likely pathogenic ★★ same condition
AGXT c.524+2T>A 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/agxt-p-cys173arg (accessed [today's date]).

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