Is AGXT p.Glu378fs (c.1129_1130dup) pathogenic?

AGXT p.Glu378fs (c.11291130dup) is classified Pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-10). Absent from gnomAD.

How common is AGXT p.Glu378fs (c.1129_1130dup) in the general population?

AGXT p.Glu378fs (c.1129_1130dup) is absent from gnomAD (gnomAD).

AGXT p.Glu378fs

c.1129_1130dup · rs2528766539 · VCV2702068

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGXT
Protein: p.Glu378fs
Coding: c.1129_1130dup
MANE Select: NM_000030
dbSNP: rs2528766539
Type: Duplication
Location: chr2:240878770 (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 378: an α-helix

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

Similar variants

AGXT c.166-1_172dup Pathogenic ★★ same type
AGXT p.Ala40fs Pathogenic/Likely pathogenic ★★ same type
AGXT p.Asp243fs Pathogenic ★★ same type
AGXT p.Tyr270fs Pathogenic/Likely pathogenic ★★ same type
AGXT p.Ala13fs Likely pathogenic ★ same type
AGXT p.Asn72fs Likely pathogenic ★ same type
AGXT p.Glu117fs Pathogenic ★ same type
AGXT p.Gly329fs 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-glu378fs (accessed [today's date]).

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