Is GRIN2A p.Pro79Arg (c.236C>G) pathogenic?

GRIN2A p.Pro79Arg (c.236C>G) is classified Likely pathogenic in GRIN2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-03-29). AlphaMissense: likely pathogenic (0.9491); Very rare (popmax 8.47e-05%, nfe); Associated with Landau-Kleffner syndrome.

What condition is associated with GRIN2A p.Pro79Arg (c.236C>G)?

GRIN2A p.Pro79Arg (c.236C>G) is associated with Landau-Kleffner syndrome, self-limited epilepsy with centrotemporal spikes (ClinVar).

How common is GRIN2A p.Pro79Arg (c.236C>G) in the general population?

GRIN2A p.Pro79Arg (c.236C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Landau-Kleffner syndrome inherited?

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

What do computational predictors say about GRIN2A p.Pro79Arg (c.236C>G)?

AlphaMissense predicts likely pathogenic (score 0.9491) — an in-silico prediction, not a clinical call.

GRIN2A p.Pro79Arg

c.236C>G · rs1250662891 · VCV433130

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9491 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Landau-Kleffner syndrome

Computational evidence

Protein change
AlphaMissense	0.9491	likely pathogenic ✓ concordant with ClinVar
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -14.26	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 371 bp · p 0.025 · regional, not allelic
Overall
CADD	28.5	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 6.2e-05% 1/1,614,206 alleles · very rare exomes 1/1,461,854 · genomes 0/152,352 · joint denominator

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.Pro79Arg
Coding: c.236C>G
MANE Select: NM_001134407
dbSNP: rs1250662891
Type: single nucleotide variant
Location: chr16:10180176 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 79: 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); a UniProt-annotated variant site (in fesd; decreased function in ion transmembrane transport when expressed in xenopus oocytes; decreased localization to cell membrane; mutant channels are less responsive to inhibition by zn(2+) than wild-type channels)

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: self-limited epilepsy with centrotemporal spikes

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-pro79arg (accessed [today's date]).

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