Is AGXT p.Leu163= (c.489G>A) pathogenic?

AGXT p.Leu163= (c.489G>A) is classified Likely benign in AGXT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). Rare (popmax 0.149%, mid); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Leu163= (c.489G>A)?

AGXT p.Leu163= (c.489G>A) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Leu163= (c.489G>A) in the general population?

AGXT p.Leu163= (c.489G>A) is rare (popmax 0.149%, mid) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Leu163=

c.489G>A · rs147601535 · VCV204040

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP -0.11, phastCons 0.99
Overall
CADD	6.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% Middle Eastern · 9/6,042 alleles

Filtering AF 0.0776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.0208% 332/1,599,146 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	671
Remaining individualsnot grpmax-eligible	0.0436%	2,294
European (non-Finnish)	0.0225%	4,445
South Asian	0.0204%	4,899
African / African-American	0.0134%	7,469
Admixed American	0.00687%	14,552

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.Leu163=
Coding: c.489G>A
MANE Select: NM_000030
dbSNP: rs147601535
Type: single nucleotide variant
Location: chr2:240871414 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB

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 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
AGXT c.595+1G>T Pathogenic ★★ same condition
AGXT c.596-2A>G 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-leu163 (accessed [today's date]).

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