Is AGXT p.Ala88= (c.264C>T) pathogenic?

AGXT p.Ala88= (c.264C>T) is classified Benign in AGXT (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 20.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ala88= (c.264C>T)?

AGXT p.Ala88= (c.264C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How is Primary hyperoxaluria inherited?

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

AGXT p.Ala88=

Q: How common is AGXT p.Ala88= (c.264C>T) in the general population?

AGXT p.Ala88= (c.264C>T) is common (popmax 20.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.264C>T · rs35698882 · VCV204030

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 20.6%, nfe) — too common for a highly-penetrant pathogenic allele

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 -13	GERP -2.5
Overall
CADD	4.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.6% European (non-Finnish) · 243,570/1,179,958 alleles

Filtering AF 20.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.5%

Overall 18.1% 292,836/1,613,658 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	25.3%	4
Finnishnot grpmax-eligible	23.8%	4
European (non-Finnish)grpmax	20.6%	5
Ashkenazi Jewishnot grpmax-eligible	17.8%	6
Remaining individualsnot grpmax-eligible	16.8%	6
Middle Eastern	16.6%	6
Admixed American	9.26%	11
South Asian	7.62%	13
African / African-American	6.05%	17
East Asian	0.0401%	2,493

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala88=
Coding: c.264C>T
MANE Select: NM_000030
dbSNP: rs35698882
Type: single nucleotide variant
Location: chr2:240869268 (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 88: 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.Ala88Thr 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
AGXT c.595+1G>T 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-ala88 (accessed [today's date]).

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