Is AGXT p.Asp254= (c.762C>T) pathogenic?

AGXT p.Asp254= (c.762C>T) is classified Likely benign in AGXT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0167%, amr); Associated with primary hyperoxaluria type 1.

What condition is associated with AGXT p.Asp254= (c.762C>T)?

AGXT p.Asp254= (c.762C>T) is associated with primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Asp254= (c.762C>T) in the general population?

AGXT p.Asp254= (c.762C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

How is Primary hyperoxaluria inherited?

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

AGXT p.Asp254=

c.762C>T · rs375038017 · VCV788848

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

primary hyperoxaluria type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.2	GERP -1.7
Overall
CADD	3.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,998 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00285% 46/1,612,876 alleles · ultra-rare exomes 37/1,460,670 · genomes 9/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
South Asian	0.0154%	6,505
African / African-American	0.012%	8,322
East Asian	0.00446%	22,444
Remaining individualsnot grpmax-eligible	0.0032%	31,224
Finnishnot grpmax-eligible	0.00156%	63,976
European (non-Finnish)	0.000679%	147,376

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.Asp254=
Coding: c.762C>T
MANE Select: NM_000030
dbSNP: rs375038017
Type: single nucleotide variant
Location: chr2:240875190 (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 254: 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.Asp254Ala Uncertain significance ★ ⚠ 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
AGXT c.595+1G>T 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-asp254 (accessed [today's date]).

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