Is GRIN2B p.Pro290= (c.870C>T) pathogenic?

GRIN2B p.Pro290= (c.870C>T) is classified Benign in GRIN2B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 8.64%, afr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, autosomal dominant 6.

What condition is associated with GRIN2B p.Pro290= (c.870C>T)?

GRIN2B p.Pro290= (c.870C>T) is associated with intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

GRIN2B p.Pro290=

Q: How common is GRIN2B p.Pro290= (c.870C>T) in the general population?

GRIN2B p.Pro290= (c.870C>T) is common (popmax 8.64%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.870C>T · rs1124894 · VCV129208

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 8.64%, afr) — too common for a highly-penetrant pathogenic allele

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 0.36	GERP -4.3, phastCons 0.59
Overall
CADD	9.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.64% African / African-American · 6,482/74,990 alleles

Filtering AF 8.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.4%

Overall 0.464% 7,486/1,613,766 alleles · common exomes 3,788/1,461,522 · genomes 3,698/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.64%	12
Remaining individualsnot grpmax-eligible	0.654%	153
Middle Eastern	0.577%	173
Admixed American	0.52%	192
South Asian	0.0209%	4,793
European (non-Finnish)	0.0192%	5,197
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801

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.Pro290=
Coding: c.870C>T
MANE Select: NM_000834
dbSNP: rs1124894
Type: single nucleotide variant
Location: chr12:13753457 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 290: an α-helix

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.Pro290Ser Benign ★ 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-pro290 (accessed [today's date]).

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