Is GRIN2B p.Arg900= (c.2700C>A) pathogenic?

GRIN2B p.Arg900= (c.2700C>A) is classified Benign in GRIN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). Ultra-rare (popmax 0.0201%, eas); Associated with intellectual disability, autosomal dominant 6.

What condition is associated with GRIN2B p.Arg900= (c.2700C>A)?

GRIN2B p.Arg900= (c.2700C>A) is associated with intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

How common is GRIN2B p.Arg900= (c.2700C>A) in the general population?

GRIN2B p.Arg900= (c.2700C>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

GRIN2B p.Arg900=

Q: How is GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder inherited?

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

c.2700C>A · rs531269037 · VCV1170662

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Conditions

intellectual disability, autosomal dominant 6

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 2.8	GERP -1.8, phastCons 1
Overall
CADD	6.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,854 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0078%

Overall 0.000805% 13/1,614,156 alleles · ultra-rare exomes 11/1,461,838 · genomes 2/152,318 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,984
South Asian	0.00439%	22,772

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.Arg900=
Coding: c.2700C>A
MANE Select: NM_000834
dbSNP: rs531269037
Type: single nucleotide variant
Location: chr12:13564538 (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

intellectual disability, autosomal dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 27

For GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal

Similar variants

GRIN2B p.Arg900Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
GRIN2B p.Arg900His 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

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-arg900 (accessed [today's date]).

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