Is AGXT p.Pro10Ser (c.28C>T) pathogenic?

AGXT p.Pro10Ser (c.28C>T) is classified Pathogenic in AGXT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-11-27). AlphaMissense: likely benign (0.2027); Very rare (popmax 0.00195%, nfe); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Pro10Ser (c.28C>T)?

AGXT p.Pro10Ser (c.28C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Pro10Ser (c.28C>T) in the general population?

AGXT p.Pro10Ser (c.28C>T) is very rare (popmax 0.00195%, 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.Pro10Ser (c.28C>T)?

AlphaMissense predicts likely benign (score 0.2027) — an in-silico prediction, not a clinical call.

AGXT p.Pro10Ser

c.28C>T · rs180177191 · VCV204068

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2027 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
AlphaMissense	0.2027	likely benign ⚠ discordant with ClinVar
REVEL	0.423	indeterminate
SaProt	LLR -13.39	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	20.8	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 0.00195% European (non-Finnish) · 23/1,179,892 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00236% 38/1,612,864 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0174%	5,739
Remaining individualsnot grpmax-eligible	0.0048%	20,821
European (non-Finnish)grpmax	0.00195%	51,300
South Asian	0.0011%	91,006

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro10Ser
Coding: c.28C>T
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.Pro10Ala Uncertain significance ★ ⚠ same residue
AGXT p.Pro10Thr Uncertain significance ★ ⚠ 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-pro10ser (accessed [today's date]).

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