Is AGXT p.Pro10Ala (c.28C>G) pathogenic?

AGXT p.Pro10Ala (c.28C>G) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 2 submitters; last evaluated 2016-02-13). AlphaMissense: likely benign (0.0906); Very rare (popmax 0.00133%, afr); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Pro10Ala (c.28C>G)?

AGXT p.Pro10Ala (c.28C>G) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Pro10Ala (c.28C>G) in the general population?

AGXT p.Pro10Ala (c.28C>G) is very rare (popmax 0.00133%, 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.Pro10Ala (c.28C>G)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

AGXT p.Pro10Ala

c.28C>G · rs180177191 · VCV383367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -10.68	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	19.82	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 0.00133% African / African-American · 1/74,932 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000806% 13/1,612,864 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,932
South Asian	0.0011%	91,006
European (non-Finnish)	0.000932%	107,263

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.Pro10Ala
Coding: c.28C>G
MANE Select: NM_000030
dbSNP: rs180177191
Type: single nucleotide variant
Location: chr2:240868893 (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 10: 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.Pro10Thr Uncertain significance ★ ⚠ same residue
AGXT p.Pro10Ser Pathogenic ⚠ same residue
AGXT p.Pro10fs 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-pro10ala (accessed [today's date]).

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