Is AGXT p.Pro11His (c.32C>A) pathogenic?

AGXT p.Pro11His (c.32C>A) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: ambiguous (0.4996); Ultra-rare (popmax 0.0736%, eas); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Pro11His (c.32C>A)?

AGXT p.Pro11His (c.32C>A) is associated with primary hyperoxaluria type 1, alanine glyoxylate aminotransferase deficiency (ClinVar).

How common is AGXT p.Pro11His (c.32C>A) in the general population?

AGXT p.Pro11His (c.32C>A) is ultra-rare (popmax 0.0736%, eas) (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.Pro11His (c.32C>A)?

AlphaMissense predicts ambiguous (score 0.4996) — an in-silico prediction, not a clinical call.

AGXT p.Pro11His

c.32C>A · rs34116584 · VCV204018

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.4996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, eas)

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.4996	ambiguous
REVEL	0.557	indeterminate
SaProt	LLR -12.65	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	23.3	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 0.0736% East Asian · 33/44,862 alleles

Filtering AF 0.0648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0632%

Overall 0.0582% 938/1,612,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0736%	1,359
European (non-Finnish)	0.0687%	1,455
Remaining individualsnot grpmax-eligible	0.056%	1,785
Admixed American	0.0317%	3,157
South Asian	0.0242%	4,138
African / African-American	0.024%	4,170

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.Pro11His
Coding: c.32C>A
MANE Select: NM_000030
dbSNP: rs34116584
Type: single nucleotide variant
Location: chr2:240868897 (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 11: an α-helix; a UniProt-annotated variant site (in allele minor; associated in cis with m-340; decreased specific alanine--glyoxylate aminotransferase activity in vitro when associated with m-340; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with i-152 and m-340; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with r-170 and m-340; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with t-244 and m-340; causes mitochondrial mistargeting when associated with r-170 and m-340)

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

Also linked: alanine glyoxylate aminotransferase deficiency

For Primary hyperoxaluria (Orphanet):

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

Similar variants

AGXT p.Pro11Ala Uncertain significance ★★ ⚠ same residue
AGXT p.Pro11Ser Uncertain significance ★★ ⚠ same residue
AGXT p.Pro11Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Pro11fs Likely pathogenic ★ same residue
AGXT p.Pro11= Likely benign ★ 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

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-pro11his (accessed [today's date]).

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