Is GRIN2B p.Pro450= (c.1350G>A) pathogenic?

GRIN2B p.Pro450= (c.1350G>A) is classified Likely benign in GRIN2B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-01). Rare (popmax 0.164%, mid); Associated with developmental and epileptic encephalopathy, 27.

What condition is associated with GRIN2B p.Pro450= (c.1350G>A)?

GRIN2B p.Pro450= (c.1350G>A) is associated with developmental and epileptic encephalopathy, 27, intellectual disability, autosomal dominant 6 (ClinVar).

How common is GRIN2B p.Pro450= (c.1350G>A) in the general population?

GRIN2B p.Pro450= (c.1350G>A) is rare (popmax 0.164%, mid) (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.Pro450=

c.1350G>A · rs200607718 · VCV702757

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.164%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.072	GERP -3, phastCons 0.96
Overall
CADD	11.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% Middle Eastern · 10/6,084 alleles

Filtering AF 0.0891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0678%

Overall 0.00384% 62/1,613,310 alleles · rare exomes 56/1,461,242 · genomes 6/152,068 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.164%	608
South Asian	0.0264%	3,794
African / African-American	0.00935%	10,696
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0048%	20,813
East Asian	0.00223%	44,874
European (non-Finnish)	0.00119%	84,247

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: GRIN2B
Protein: p.Pro450=
Coding: c.1350G>A
MANE Select: NM_000834
dbSNP: rs200607718
Type: single nucleotide variant
Location: chr12:13615643 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB

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.Pro450Leu Uncertain significance ★★ ⚠ 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
GRIN2B p.Arg393Ter 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-pro450 (accessed [today's date]).

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