Is AGXT p.Ile279Thr (c.836T>C) pathogenic?

AGXT p.Ile279Thr (c.836T>C) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2204); Rare (popmax 0.356%, nfe); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ile279Thr (c.836T>C)?

AGXT p.Ile279Thr (c.836T>C) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ile279Thr (c.836T>C) in the general population?

AGXT p.Ile279Thr (c.836T>C) is rare (popmax 0.356%, nfe) (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.Ile279Thr (c.836T>C)?

AlphaMissense predicts likely benign (score 0.2204) — an in-silico prediction, not a clinical call.

AGXT p.Ile279Thr

c.836T>C · rs140992177 · VCV198686

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.2204 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.356%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.2204	likely benign
REVEL	0.551	indeterminate
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.356% European (non-Finnish) · 4,205/1,179,988 alleles

Filtering AF 0.347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.344%

Overall 0.29% 4,677/1,614,098 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.356%	281
South Asian	0.235%	426
Remaining individualsnot grpmax-eligible	0.227%	440
Middle Eastern	0.099%	1,010
Finnishnot grpmax-eligible	0.0656%	1,524
Admixed American	0.0483%	2,070
African / African-American	0.0373%	2,680
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,290
East Asian	0.00446%	22,438

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.Ile279Thr
Coding: c.836T>C
MANE Select: NM_000030
dbSNP: rs140992177
Type: single nucleotide variant
Location: chr2:240875994 (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 279: a UniProt-annotated variant site (in hp1); a UniProt-annotated variant site (in); 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.Ile279Met Uncertain significance ⚠ same residue
AGXT p.Ile279fs Pathogenic same residue
AGXT p.Ile279= 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

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-ile279thr (accessed [today's date]).

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