Is AGXT p.Ala296= (c.888G>A) pathogenic?

AGXT p.Ala296= (c.888G>A) is classified Likely benign in AGXT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-14). Very rare (popmax 0.00588%, amr); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ala296= (c.888G>A)?

AGXT p.Ala296= (c.888G>A) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ala296= (c.888G>A) in the general population?

AGXT p.Ala296= (c.888G>A) is very rare (popmax 0.00588%, amr) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Ala296=

c.888G>A · rs979513298 · VCV763755

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00588%, amr)

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 -16	GERP -2.3
Overall
CADD	0.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00588% Admixed American · 3/50,978 alleles

Filtering AF 0.00202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00173%

Overall 0.00264% 41/1,550,786 alleles · very rare exomes 32/1,398,534 · genomes 9/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00588%	16,993
African / African-American	0.00411%	24,359
Remaining individualsnot grpmax-eligible	0.00333%	30,043
European (non-Finnish)	0.00279%	35,842
South Asian	0.00119%	84,066

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.Ala296=
Coding: c.888G>A
MANE Select: NM_000030
dbSNP: rs979513298
Type: single nucleotide variant
Location: chr2:240877578 (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 296: a UniProt-annotated variant site (in hp1); 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.Ala296Val Uncertain significance ★★ ⚠ same residue
AGXT p.Ala296del Conflicting classifications of pathogenicity ★ 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-ala296 (accessed [today's date]).

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