Is AGXT p.Ala248Ser (c.742G>T) pathogenic?

AGXT p.Ala248Ser (c.742G>T) is classified Conflicting classifications of pathogenicity in AGXT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1219); Very rare (popmax 0.00805%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGXT p.Ala248Ser (c.742G>T)?

AGXT p.Ala248Ser (c.742G>T) is associated with Inborn genetic diseases, primary hyperoxaluria type 1 (ClinVar).

How common is AGXT p.Ala248Ser (c.742G>T) in the general population?

AGXT p.Ala248Ser (c.742G>T) is very rare (popmax 0.00805%, nfe) (gnomAD).

What do computational predictors say about AGXT p.Ala248Ser (c.742G>T)?

AlphaMissense predicts likely benign (score 0.1219) — an in-silico prediction, not a clinical call.

AGXT p.Ala248Ser

c.742G>T · rs180177260 · VCV204048

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1219 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1219	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -9.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.84, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	18.18	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 0.00805% European (non-Finnish) · 95/1,179,862 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00601% 97/1,613,852 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00805%	12,420
Remaining individualsnot grpmax-eligible	0.0032%	31,235

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.Ala248Ser
Coding: c.742G>T
MANE Select: NM_000030
dbSNP: rs180177260
Type: single nucleotide variant
Location: chr2:240875170 (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 248: an α-helix

Full AGXT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary hyperoxaluria type 1

Similar variants

AGXT p.Ala248Val Conflicting classifications of pathogenicity ★ ⚠ same residue
AGXT p.Ala248= 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

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-ala248ser (accessed [today's date]).

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