Is AGXT p.Arg317Trp (c.949C>T) pathogenic?

AGXT p.Arg317Trp (c.949C>T) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.3061); Ultra-rare (popmax 0.0267%, amr); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Arg317Trp (c.949C>T)?

AGXT p.Arg317Trp (c.949C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Arg317Trp (c.949C>T) in the general population?

AGXT p.Arg317Trp (c.949C>T) is ultra-rare (popmax 0.0267%, amr) (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.Arg317Trp (c.949C>T)?

AlphaMissense predicts likely benign (score 0.3061) — an in-silico prediction, not a clinical call.

AGXT p.Arg317Trp

c.949C>T · rs774030578 · VCV631851

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.3061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.3061	likely benign
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -12.33	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.45	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.9	GERP 1.2, phastCons 0.16
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

Grpmax group 0.0267% Admixed American · 16/60,002 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00366% 59/1,611,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0112%	8,924
European (non-Finnish)	0.00288%	34,706
South Asian	0.0022%	45,543

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.Arg317Trp
Coding: c.949C>T
MANE Select: NM_000030
dbSNP: rs774030578
Type: single nucleotide variant
Location: chr2:240878028 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB

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.Arg317Gln Uncertain significance ★★ ⚠ same residue
AGXT p.Arg317Pro 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

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-arg317trp (accessed [today's date]).

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