Is GRIN2A p.Asp294= (c.882C>T) pathogenic?

GRIN2A p.Asp294= (c.882C>T) is classified Benign/Likely benign in GRIN2A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-16). Very rare (popmax 0.00892%, eas); Associated with Landau-Kleffner syndrome.

What condition is associated with GRIN2A p.Asp294= (c.882C>T)?

GRIN2A p.Asp294= (c.882C>T) is associated with Landau-Kleffner syndrome, GRIN2A-related complex neurodevelopmental disorder (ClinVar).

How common is GRIN2A p.Asp294= (c.882C>T) in the general population?

GRIN2A p.Asp294= (c.882C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

How is Landau-Kleffner syndrome inherited?

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

GRIN2A p.Asp294=

c.882C>T · rs201002710 · VCV377936

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

Landau-Kleffner syndrome

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 -8	GERP -3.8
Overall
CADD	1.175	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,824 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00297% 48/1,613,766 alleles · very rare exomes 37/1,461,532 · genomes 11/152,234 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,206
African / African-American	0.00533%	18,760
Remaining individualsnot grpmax-eligible	0.0048%	20,831
European (non-Finnish)	0.00314%	31,885

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: GRIN2A
Protein: p.Asp294=
Coding: c.882C>T
MANE Select: NM_001134407
dbSNP: rs201002710
Type: single nucleotide variant
Location: chr16:9938084 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 294: an α-helix; a UniProt-annotated variant site (found in schizophrenia; uncertain significance; loss of function in ion transmembrane transport; the channel is not activated by glutamate)

Full GRIN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Landau-Kleffner syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GRIN2A-related complex neurodevelopmental disorder

For Landau-Kleffner syndrome (Orphanet):

Inheritance: Autosomal dominant, Unknown
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

GRIN2A c.1007+1G>A Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.1007+1G>T Pathogenic ★★ same condition
GRIN2A c.1123-2A>G Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.1497+1G>T Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.2007+1G>T Likely pathogenic ★★ same condition
GRIN2A c.2168+1G>C Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.415-2A>G Likely pathogenic ★★ same condition
GRIN2A p.Ala548Pro Likely pathogenic ★★ 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/grin2a-p-asp294 (accessed [today's date]).

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