Is AGXT p.Thr355= (c.1065G>A) pathogenic?

AGXT p.Thr355= (c.1065G>A) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.02%, eas); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Thr355= (c.1065G>A)?

AGXT p.Thr355= (c.1065G>A) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Thr355= (c.1065G>A) in the general population?

AGXT p.Thr355= (c.1065G>A) is ultra-rare (popmax 0.02%, eas) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Thr355=

c.1065G>A · rs143488099 · VCV1448578

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

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 -2	GERP -2.3
Overall
CADD	2.326	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% East Asian · 9/44,896 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00143% 23/1,612,822 alleles · ultra-rare exomes 20/1,460,616 · genomes 3/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
Remaining individualsnot grpmax-eligible	0.0048%	20,824
South Asian	0.0022%	45,543
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000678%	147,495

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.Thr355=
Coding: c.1065G>A
MANE Select: NM_000030
dbSNP: rs143488099
Type: single nucleotide variant
Location: chr2:240878144 (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 355: 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.Thr355Lys Uncertain significance ★ ⚠ same residue
AGXT p.Thr355Met Uncertain significance ★ ⚠ 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-thr355 (accessed [today's date]).

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