Is AGXT p.Arg197Gln (c.590G>A) pathogenic?

AGXT p.Arg197Gln (c.590G>A) is classified Benign/Likely benign in AGXT (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.071); Common (popmax 7.62%, eas) — too common for a highly-penetrant pathogenic allele; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Arg197Gln (c.590G>A)?

AGXT p.Arg197Gln (c.590G>A) is associated with primary hyperoxaluria type 1 (ClinVar).

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.Arg197Gln (c.590G>A)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

AGXT p.Arg197Gln

Q: How common is AGXT p.Arg197Gln (c.590G>A) in the general population?

AGXT p.Arg197Gln (c.590G>A) is common (popmax 7.62%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.590G>A · rs34664134 · VCV92312

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.62%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -4.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	12.27	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

Grpmax group 7.62% East Asian · 3,414/44,832 alleles

Filtering AF 7.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.32%

Overall 0.453% 7,305/1,613,450 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.62%	13
South Asian	2.79%	36
Remaining individualsnot grpmax-eligible	0.53%	189
Admixed American	0.408%	245
Middle Eastern	0.165%	606
Finnishnot grpmax-eligible	0.0769%	1,300
European (non-Finnish)	0.0587%	1,705
African / African-American	0.028%	3,572
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594

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: AGXT
Protein: p.Arg197Gln
Coding: c.590G>A
MANE Select: NM_000030
dbSNP: rs34664134
Type: single nucleotide variant
Location: chr2:240873044 (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 197: a turn

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.Arg197Trp Uncertain significance ★ ⚠ same residue
AGXT p.Arg197= 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
AGXT c.525-1G>A Pathogenic ★★ same condition
AGXT c.525-2A>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/agxt-p-arg197gln (accessed [today's date]).

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