Is AGXT p.Ser187Phe (c.560C>T) pathogenic?

AGXT p.Ser187Phe (c.560C>T) is classified Pathogenic in AGXT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-03-26). AlphaMissense: likely pathogenic (0.8329); Very rare (popmax 0.000254%, nfe); Associated with primary hyperoxaluria.

What condition is associated with AGXT p.Ser187Phe (c.560C>T)?

AGXT p.Ser187Phe (c.560C>T) is associated with primary hyperoxaluria, primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ser187Phe (c.560C>T) in the general population?

AGXT p.Ser187Phe (c.560C>T) is very rare (popmax 0.000254%, 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.Ser187Phe (c.560C>T)?

AlphaMissense predicts likely pathogenic (score 0.8329) — an in-silico prediction, not a clinical call.

AGXT p.Ser187Phe

c.560C>T · rs180177238 · VCV140584

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary hyperoxaluria

Computational evidence

Protein change
AlphaMissense	0.8329	likely pathogenic ✓ concordant with ClinVar
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.98, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	24.6	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 0.000254% European (non-Finnish) · 3/1,179,954 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00197% 3/152,172 alleles · very rare

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.Ser187Phe
Coding: c.560C>T
MANE Select: NM_000030
dbSNP: rs180177238
Type: single nucleotide variant
Location: chr2:240873014 (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 187: a UniProt-annotated variant site (in hp1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization but improved dimerization in the presence of pyridoxal phosphate; decreased protein stability); a turn

Full AGXT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary hyperoxaluria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary hyperoxaluria type 1

For Primary hyperoxaluria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Germany)

Similar variants

AGXT p.Ser187Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Ser187_Leu188insVal 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
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-ser187phe (accessed [today's date]).

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