Is GRIN2B p.Arg682= (c.2046C>G) pathogenic?

GRIN2B p.Arg682= (c.2046C>G) is classified Likely benign in GRIN2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 27.

What condition is associated with GRIN2B p.Arg682= (c.2046C>G)?

GRIN2B p.Arg682= (c.2046C>G) is associated with developmental and epileptic encephalopathy, 27, intellectual disability, autosomal dominant 6 (ClinVar).

How common is GRIN2B p.Arg682= (c.2046C>G) in the general population?

GRIN2B p.Arg682= (c.2046C>G) is absent from gnomAD v4.1 (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

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

GRIN2B p.Arg682=

c.2046C>G · rs1057522130 · VCV385126

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental and epileptic encephalopathy, 27

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 3.4	GERP -0.11, phastCons 1
Overall
CADD	8.905	PHRED · no single calibrated threshold — expert panels disagree

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: GRIN2B
Protein: p.Arg682=
Coding: c.2046C>G
MANE Select: NM_000834
dbSNP: rs1057522130
Type: single nucleotide variant
Location: chr12:13571929 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 682: a UniProt-annotated variant site (in mrd6; decreased protein abundance; no effect on localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol; analysis of agonist dose-response curves for glutamate and glycine are not consistent)

Full GRIN2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, autosomal dominant 6

For Infantile epileptic spasms syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant

Similar variants

GRIN2B p.Arg682Cys Pathogenic/Likely pathogenic ★★ same residue
GRIN2B p.Arg682His Pathogenic/Likely pathogenic ★★ same residue
GRIN2B c.2172-2A>G Pathogenic ★★ same condition
GRIN2B p.Ala639Val Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Ala644Asp Pathogenic ★★ same condition
GRIN2B p.Ala734Val Likely pathogenic ★★ same condition
GRIN2B p.Ala819Thr Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Arg1111His Pathogenic/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/grin2b-p-arg682 (accessed [today's date]).

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