Is AGXT p.Ala280Val (c.839C>T) pathogenic?

AGXT p.Ala280Val (c.839C>T) is classified Benign/Likely benign in AGXT (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.139); Low-frequency (popmax 3.64%, afr); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ala280Val (c.839C>T)?

AGXT p.Ala280Val (c.839C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ala280Val (c.839C>T) in the general population?

AGXT p.Ala280Val (c.839C>T) is low-frequency (popmax 3.64%, afr) (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.Ala280Val (c.839C>T)?

AlphaMissense predicts likely benign (score 0.139) — an in-silico prediction, not a clinical call.

AGXT p.Ala280Val

c.839C>T · rs73106685 · VCV204052

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.139 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.64%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.139	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.8	GERP -2.6
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	6.04	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 3.64% African / African-American · 2,735/75,042 alleles

Filtering AF 3.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.48%

Overall 0.196% 3,164/1,614,066 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.64%	27
Admixed American	0.308%	324
Remaining individualsnot grpmax-eligible	0.232%	431
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.00737%	13,563
South Asian	0.00659%	15,177
East Asian	0.00223%	44,874

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.Ala280Val
Coding: c.839C>T
MANE Select: NM_000030
dbSNP: rs73106685
Type: single nucleotide variant
Location: chr2:240875997 (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 280: 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.Ala280fs Likely pathogenic ★ same residue
AGXT p.Ala280= 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-ala280val (accessed [today's date]).

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