Is GLUL p.Arg299= (c.897T>C) pathogenic?

GLUL p.Arg299= (c.897T>C) is classified Likely benign in GLUL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). Absent from gnomAD v4.1; Associated with congenital brain dysgenesis due to glutamine synthetase deficiency.

What condition is associated with GLUL p.Arg299= (c.897T>C)?

GLUL p.Arg299= (c.897T>C) is associated with congenital brain dysgenesis due to glutamine synthetase deficiency (ClinVar).

How common is GLUL p.Arg299= (c.897T>C) in the general population?

GLUL p.Arg299= (c.897T>C) is absent from gnomAD v4.1 (gnomAD).

GLUL p.Arg299=

Q: How is Congenital brain dysgenesis due to glutamine synthetase deficiency inherited?

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

c.897T>C · VCV3690302

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital brain dysgenesis due to glutamine synthetase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2.3, phastCons 1
Overall
CADD	11.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GLUL
Protein: p.Arg299=
Coding: c.897T>C
MANE Select: NM_001033044
Type: single nucleotide variant
Location: chr1:182384630 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.58 · 12 PDB
Residue 299: the gs catalytic domain; an α-helix

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

Disease context

congenital brain dysgenesis due to glutamine synthetase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital brain dysgenesis due to glutamine synthetase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GLUL p.Arg299His Uncertain significance ★ ⚠ same residue
GLUL p.Arg299Leu Uncertain significance ★ ⚠ same residue
GLUL c.*129G>T Uncertain significance ★★ same condition
GLUL c.*272C>G Uncertain significance ★★ same condition
GLUL c.*849C>T Uncertain significance ★★ same condition
GLUL p.Arg181Gln Uncertain significance ★★ ⚠ same condition
GLUL p.Arg286His Uncertain significance ★★ ⚠ same condition
GLUL p.Arg357Cys Uncertain significance ★★ ⚠ 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/glul-p-arg299 (accessed [today's date]).

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