Is AGXT p.Ser81Trp (c.242C>G) pathogenic?

AGXT p.Ser81Trp (c.242C>G) is classified Likely pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: likely pathogenic (0.9177); Absent from gnomAD v4.1; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ser81Trp (c.242C>G)?

AGXT p.Ser81Trp (c.242C>G) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ser81Trp (c.242C>G) in the general population?

AGXT p.Ser81Trp (c.242C>G) 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.Ser81Trp (c.242C>G)?

AlphaMissense predicts likely pathogenic (score 0.9177) — an in-silico prediction, not a clinical call.

AGXT p.Ser81Trp

c.242C>G · rs180177184 · VCV2681156

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.9177	likely pathogenic ✓ concordant with ClinVar · top 5% in AGXT
REVEL	0.836	moderately pathogenic-leaning
SaProt	LLR -15.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.60 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGXT
Protein: p.Ser81Trp
Coding: c.242C>G
MANE Select: NM_000030
dbSNP: rs180177184
Type: single nucleotide variant
Location: chr2:240869246 (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.Ser81Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
AGXT p.Ser81= Conflicting classifications of pathogenicity ★ same residue
AGXT p.Ser81Ter Pathogenic 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-ser81trp (accessed [today's date]).

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