Is AGXT p.Ser218= (c.654G>A) pathogenic?

AGXT p.Ser218= (c.654G>A) is classified Benign/Likely benign in AGXT (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 20%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Ser218= (c.654G>A)?

AGXT p.Ser218= (c.654G>A) is associated with primary hyperoxaluria type 1 (ClinVar).

How is Primary hyperoxaluria inherited?

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

AGXT p.Ser218=

Q: How common is AGXT p.Ser218= (c.654G>A) in the general population?

AGXT p.Ser218= (c.654G>A) is common (popmax 20%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.654G>A · rs33958047 · VCV198034

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 20%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.7	GERP -2.2
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20% African / African-American · 14,987/74,962 alleles

Filtering AF 19.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.6%

Overall 10.9% 175,057/1,613,208 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20%	5
East Asian	15.7%	6
South Asian	12.2%	8
Remaining individualsnot grpmax-eligible	11.7%	9
Middle Eastern	11.6%	9
European (non-Finnish)	10.3%	10
Ashkenazi Jewishnot grpmax-eligible	9.48%	11
Finnishnot grpmax-eligible	8.83%	11
Admixed American	5.85%	17
Amishnot grpmax-eligible	4.18%	24

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.Ser218=
Coding: c.654G>A
MANE Select: NM_000030
dbSNP: rs33958047
Type: single nucleotide variant
Location: chr2:240874036 (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 218: a UniProt-annotated variant site (in hp1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; no effect on protein stability); a β-strand

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.Ser218Leu Pathogenic ★★ same residue
AGXT p.Ser218Ter Likely 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
AGXT c.525-2A>T 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-ser218 (accessed [today's date]).

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