Is GRIN2A p.Ser511= (c.1533G>A) pathogenic?

GRIN2A p.Ser511= (c.1533G>A) is classified Likely benign in GRIN2A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0414%, afr); Associated with Landau-Kleffner syndrome.

What condition is associated with GRIN2A p.Ser511= (c.1533G>A)?

GRIN2A p.Ser511= (c.1533G>A) is associated with Landau-Kleffner syndrome, GRIN2A-related complex neurodevelopmental disorder (ClinVar).

How common is GRIN2A p.Ser511= (c.1533G>A) in the general population?

GRIN2A p.Ser511= (c.1533G>A) is ultra-rare (popmax 0.0414%, afr) (gnomAD).

How is Landau-Kleffner syndrome inherited?

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

GRIN2A p.Ser511=

c.1533G>A · rs112848130 · VCV386654

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0414%, afr)

Conditions

Landau-Kleffner syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.017	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0414% African / African-American · 29/70,004 alleles

Filtering AF 0.0296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0256%

Overall 0.00768% 123/1,600,972 alleles · ultra-rare exomes 108/1,460,332 · genomes 15/140,640 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0414%	2,414
Remaining individualsnot grpmax-eligible	0.0289%	3,457
Middle Eastern	0.0167%	5,988
Admixed American	0.0121%	8,252
South Asian	0.00552%	18,129
European (non-Finnish)	0.00518%	19,306
East Asian	0.00449%	22,253

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.Ser511=
Coding: c.1533G>A
MANE Select: NM_001134407
dbSNP: rs112848130
Type: single nucleotide variant
Location: chr16:9840765 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 511: a binding site; 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 p.Ser511Leu Pathogenic/Likely pathogenic ★★ same residue
GRIN2A p.Ser511fs Pathogenic ★ same residue
GRIN2A p.Ser511Ter Pathogenic ★ same residue
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

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-ser511 (accessed [today's date]).

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