Is GLUL p.Ser350= (c.1050G>A) pathogenic?

GLUL p.Ser350= (c.1050G>A) is classified Likely benign in GLUL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Ultra-rare (popmax 0.0132%, sas); Associated with congenital brain dysgenesis due to glutamine synthetase deficiency.

What condition is associated with GLUL p.Ser350= (c.1050G>A)?

GLUL p.Ser350= (c.1050G>A) is associated with congenital brain dysgenesis due to glutamine synthetase deficiency (ClinVar).

How common is GLUL p.Ser350= (c.1050G>A) in the general population?

GLUL p.Ser350= (c.1050G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

GLUL p.Ser350=

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.1050G>A · rs763261567 · VCV1391817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

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 -9.6	GERP -4.1
Overall
CADD	4.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,068 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00167% 27/1,613,816 alleles · ultra-rare exomes 27/1,461,638 · genomes 0/152,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,589
European (non-Finnish)	0.00127%	78,655

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: GLUL
Protein: p.Ser350=
Coding: c.1050G>A
MANE Select: NM_001033044
dbSNP: rs763261567
Type: single nucleotide variant
Location: chr1:182384477 (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 350: 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.Ser350Leu 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
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-ser350 (accessed [today's date]).

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