Is AGXT p.Lys229del (c.683AGA[1]) pathogenic?

AGXT p.Lys229del (c.683AGA[1]) is classified Likely pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Very rare (popmax 0.00034%, nfe); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Lys229del (c.683AGA[1])?

AGXT p.Lys229del (c.683AGA[1]) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Lys229del (c.683AGA[1]) in the general population?

AGXT p.Lys229del (c.683AGA[1]) is very rare (popmax 0.00034%, nfe) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Lys229del

c.683AGA[1] · rs1553648979 · VCV801921

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

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 · substitutions only
Constraint at this position
Conservation	phyloP 0.075	GERP -1.7
Overall
CADD	17.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,176,270 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,609,844 alleles · very rare

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.Lys229del
Coding: c.683AGA[1]
MANE Select: NM_000030
dbSNP: rs1553648979
Type: Microsatellite
Location: chr2:240875110 (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 229: 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.Lys229dup Uncertain significance same residue
AGXT p.Ala85fs Pathogenic/Likely pathogenic ★★ same condition
AGXT p.Val324fs Pathogenic ★★ same condition
AGXT c.358+56_358+64del Benign ★★ same condition
AGXT c.165+15_165+16insTCGCTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGTAGGGAAGGGGGTCACTGCTTCC Uncertain significance ★ same condition
AGXT p.Ala296del Conflicting classifications of pathogenicity ★ same condition
AGXT p.Asn372fs Uncertain significance ★ same condition
AGXT p.Lys229= Likely benign ★ same residue

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-lys229del (accessed [today's date]).

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