Is AGXT p.Glu138Val (c.413A>T) pathogenic?

AGXT p.Glu138Val (c.413A>T) is classified Uncertain significance in AGXT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-24). AlphaMissense: ambiguous (0.4679); Absent from gnomAD v4.1; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Glu138Val (c.413A>T)?

AGXT p.Glu138Val (c.413A>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Glu138Val (c.413A>T) in the general population?

AGXT p.Glu138Val (c.413A>T) is absent from gnomAD v4.1 (gnomAD).

How is Primary hyperoxaluria inherited?

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

What do computational predictors say about AGXT p.Glu138Val (c.413A>T)?

AlphaMissense predicts ambiguous (score 0.4679) — an in-silico prediction, not a clinical call.

AGXT p.Glu138Val

c.413A>T · VCV4069056

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4679 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,552,512)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.4679	ambiguous
REVEL	0.733	pathogenic-leaning
SaProt	LLR -14.90	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,552,512). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGXT
Protein: p.Glu138Val
Coding: c.413A>T
MANE Select: NM_000030
Type: single nucleotide variant
Location: chr2:240870698 (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 138: 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.Glu138Ter Likely pathogenic ★ same residue
AGXT p.Glu138= Likely benign ★ 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-glu138val (accessed [today's date]).

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