Is AGXT p.Asp334= (c.1002C>T) pathogenic?

AGXT p.Asp334= (c.1002C>T) is classified Likely benign in AGXT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-03). Ultra-rare (popmax 0.012%, afr); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Asp334= (c.1002C>T)?

AGXT p.Asp334= (c.1002C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Asp334= (c.1002C>T) in the general population?

AGXT p.Asp334= (c.1002C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Asp334=

c.1002C>T · rs370897272 · VCV1354545

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

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 3	GERP -0.073, phastCons 1
Overall
CADD	7.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,916 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000682% 11/1,613,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,324
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Asp334=
Coding: c.1002C>T
MANE Select: NM_000030
dbSNP: rs370897272
Type: single nucleotide variant
Location: chr2:240878081 (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 334: 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 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-asp334 (accessed [today's date]).

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