Is AGXT p.Arg118Cys (c.352C>T) pathogenic?

AGXT p.Arg118Cys (c.352C>T) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-06-22). AlphaMissense: ambiguous (0.398); Very rare (popmax 0.00779%, nfe); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Arg118Cys (c.352C>T)?

AGXT p.Arg118Cys (c.352C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Arg118Cys (c.352C>T) in the general population?

AGXT p.Arg118Cys (c.352C>T) is very rare (popmax 0.00779%, 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.Arg118Cys (c.352C>T)?

AlphaMissense predicts ambiguous (score 0.398) — an in-silico prediction, not a clinical call.

AGXT p.Arg118Cys

c.352C>T · rs376844297 · VCV204095

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.398 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00779%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.398	ambiguous
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -12.00	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	29.3	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 0.00779% European (non-Finnish) · 91/1,167,544 alleles

Filtering AF 0.00646% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00598%

Overall 0.00654% 104/1,591,258 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00811%	12,332
European (non-Finnish)grpmax	0.00779%	12,830
South Asian	0.00576%	17,372
East Asian	0.00224%	44,716
Admixed American	0.00169%	59,118
African / African-American	0.00134%	74,678

Remaining individuals 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.Arg118Cys
Coding: c.352C>T
MANE Select: NM_000030
dbSNP: rs376844297
Type: single nucleotide variant
Location: chr2:240869356 (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 118: 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.Arg118His Likely pathogenic ★ ⚠ same residue
AGXT p.Arg118Ser Likely pathogenic ★ same residue
AGXT p.Arg118Pro 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

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-arg118cys (accessed [today's date]).

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