Is GLUL p.Arg324Ser (c.970C>A) pathogenic?

GLUL p.Arg324Ser (c.970C>A) is classified Pathogenic in GLUL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2011-05-01). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with congenital brain dysgenesis due to glutamine synthetase deficiency.

What condition is associated with GLUL p.Arg324Ser (c.970C>A)?

GLUL p.Arg324Ser (c.970C>A) is associated with congenital brain dysgenesis due to glutamine synthetase deficiency (ClinVar).

How common is GLUL p.Arg324Ser (c.970C>A) in the general population?

GLUL p.Arg324Ser (c.970C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLUL p.Arg324Ser (c.970C>A)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

GLUL p.Arg324Ser

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.970C>A · rs80358214 · VCV29734

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital brain dysgenesis due to glutamine synthetase deficiency

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic ✓ concordant with ClinVar · top 2% in GLUL
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -12.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 182 bp · p 0.00086 · regional, not allelic
Overall
CADD	29.7	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

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.Arg324Ser
Coding: c.970C>A
MANE Select: NM_001033044
dbSNP: rs80358214
Type: single nucleotide variant
Location: chr1:182384557 (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 324: a binding site; a UniProt-annotated variant site (in glnd; reduced glutamine synthetase activity; decreased function in ribosomal 40s subunit synthesis associated with loss of nucleolar location of bysl); the gs catalytic domain; a β-strand

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.Arg324Cys Pathogenic 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
GLUL p.Arg90Cys 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-arg324ser (accessed [today's date]).

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