Is AGXT p.Ala328Ser (c.982G>T) pathogenic?

AGXT p.Ala328Ser (c.982G>T) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.081); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with AGXT p.Ala328Ser (c.982G>T)?

AGXT p.Ala328Ser (c.982G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AGXT p.Ala328Ser (c.982G>T) in the general population?

AGXT p.Ala328Ser (c.982G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about AGXT p.Ala328Ser (c.982G>T)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

AGXT p.Ala328Ser

c.982G>T · VCV4253684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -5.65	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 -0.082	GERP -2.3
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	1.928	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00031% 5/1,612,888 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
European (non-Finnish)	0.000254%	393,335

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.Ala328Ser
Coding: c.982G>T
MANE Select: NM_000030
Type: single nucleotide variant
Location: chr2:240878061 (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

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

Similar variants

AGXT p.Ala328Thr Uncertain significance ★★ ⚠ same residue
AGXT p.Ala328= Likely benign ★ same residue
AGXT p.Ser81Leu Pathogenic/Likely pathogenic ★★ same condition
AGXT c.847-3C>T Uncertain significance ★★ same condition
AGXT p.Ala296Val Uncertain significance ★★ ⚠ same condition
AGXT p.Ala382Val Uncertain significance ★★ ⚠ same condition
AGXT p.Val266Ile Uncertain significance ★★ ⚠ same condition
AGXT p.Ala328_Tyr330delinsAsp Likely pathogenic ★ same residue

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-ala328ser (accessed [today's date]).

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