Is AGXT p.Ala328= (c.984T>G) pathogenic?

AGXT p.Ala328= (c.984T>G) is classified Likely benign in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-09). Very rare (popmax 0.0011%, sas).

How common is AGXT p.Ala328= (c.984T>G) in the general population?

AGXT p.Ala328= (c.984T>G) is very rare (popmax 0.0011%, sas) (gnomAD).

AGXT p.Ala328=

c.984T>G · rs2059037792 · VCV1079731

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 · T>A here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.8	GERP -2.3
Overall
CADD	0.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 0.000137% 2/1,460,898 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,008

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.Ala328=
Coding: c.984T>G
MANE Select: NM_000030
dbSNP: rs2059037792
Type: single nucleotide variant
Location: chr2:240878063 (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

Similar variants

AGXT p.Ala328Thr Uncertain significance ★★ ⚠ same residue
AGXT p.Ala328Ser Uncertain significance ★ ⚠ same residue
AGXT p.Ala328_Tyr330delinsAsp Likely pathogenic ★ same residue
AGXT c.358+1G>A Pathogenic ★★ same type
AGXT c.359-2A>G Likely pathogenic ★★ same type
AGXT c.423+1G>A Pathogenic/Likely pathogenic ★★ same type
AGXT c.524+2T>A Likely pathogenic ★★ same type
AGXT c.525-1G>A Pathogenic ★★ same type

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-ala328 (accessed [today's date]).

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