Is GRIN2B p.Val280= (c.840A>G) pathogenic?

GRIN2B p.Val280= (c.840A>G) is classified Likely benign in GRIN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 0.00133%, afr); Associated with intellectual disability, autosomal dominant 6.

What condition is associated with GRIN2B p.Val280= (c.840A>G)?

GRIN2B p.Val280= (c.840A>G) is associated with intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

How common is GRIN2B p.Val280= (c.840A>G) in the general population?

GRIN2B p.Val280= (c.840A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

GRIN2B p.Val280=

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.840A>G · rs752814750 · VCV1084748

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 -0.83	GERP -4.3, phastCons 0.006
Overall
CADD	5.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,052 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000867% 14/1,614,168 alleles · very rare exomes 14/1,461,834 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,835
African / African-Americangrpmax	0.00133%	75,052
European (non-Finnish)	0.000847%	118,001

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val280=
Coding: c.840A>G
MANE Select: NM_000834
dbSNP: rs752814750
Type: single nucleotide variant
Location: chr12:13753487 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 280: a β-strand

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 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
GRIN2B p.Arg519Gln 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-val280 (accessed [today's date]).

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