Is AGXT p.Pro10Thr (c.28C>A) pathogenic?

AGXT p.Pro10Thr (c.28C>A) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-06). AlphaMissense: likely benign (0.1725); Ultra-rare (popmax 0.049%, eas); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Pro10Thr (c.28C>A)?

AGXT p.Pro10Thr (c.28C>A) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Pro10Thr (c.28C>A) in the general population?

AGXT p.Pro10Thr (c.28C>A) is ultra-rare (popmax 0.049%, 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.Pro10Thr (c.28C>A)?

AlphaMissense predicts likely benign (score 0.1725) — an in-silico prediction, not a clinical call.

AGXT p.Pro10Thr

c.28C>A · VCV3586199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1725 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.1725	likely benign
REVEL	0.474	indeterminate
SaProt	LLR -12.43	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	20.6	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 0.049% East Asian · 22/44,860 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00291% 47/1,612,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,039
South Asian	0.00659%	15,167
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00127%	78,659

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.Pro10Thr
Coding: c.28C>A
MANE Select: NM_000030
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.Pro10Ala 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-pro10thr (accessed [today's date]).

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