Is AGXT p.Ser81= (c.243G>A) pathogenic?

AGXT p.Ser81= (c.243G>A) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-31). Rare (popmax 0.132%, mid); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ser81= (c.243G>A)?

AGXT p.Ser81= (c.243G>A) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ser81= (c.243G>A) in the general population?

AGXT p.Ser81= (c.243G>A) is rare (popmax 0.132%, mid) (gnomAD).

How is Primary hyperoxaluria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGXT p.Ser81=

c.243G>A · rs145135990 · VCV1117136

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.42	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -20	GERP -2.5
Overall
CADD	0.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00632% 102/1,613,796 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
African / African-American	0.0666%	1,501
South Asian	0.0121%	8,280
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00333%	30,006
European (non-Finnish)	0.00203%	49,166

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.Ser81=
Coding: c.243G>A
MANE Select: NM_000030
dbSNP: rs145135990
Type: single nucleotide variant
Location: chr2:240869247 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB

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.Ser81Leu Pathogenic/Likely pathogenic ★★ same residue
AGXT p.Ser81Trp Likely pathogenic ★ same residue
AGXT p.Ser81Ter 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-ser81 (accessed [today's date]).

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