Is GRIN2B p.Pro887= (c.2661C>A) pathogenic?

GRIN2B p.Pro887= (c.2661C>A) is classified Likely benign in GRIN2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-01). Very rare (popmax 0.0039%, nfe); Associated with intellectual disability, autosomal dominant 6.

What condition is associated with GRIN2B p.Pro887= (c.2661C>A)?

GRIN2B p.Pro887= (c.2661C>A) is associated with intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

How common is GRIN2B p.Pro887= (c.2661C>A) in the general population?

GRIN2B p.Pro887= (c.2661C>A) is very rare (popmax 0.0039%, nfe) (gnomAD).

GRIN2B p.Pro887=

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.2661C>A · rs201157664 · VCV1133487

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

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 0.25	GERP -0.46, phastCons 0.94
Overall
CADD	6.492	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% European (non-Finnish) · 46/1,179,932 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00291% 47/1,613,844 alleles · very rare exomes 41/1,461,698 · genomes 6/152,146 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,651
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Pro887=
Coding: c.2661C>A
MANE Select: NM_000834
dbSNP: rs201157664
Type: single nucleotide variant
Location: chr12:13564577 (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 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-pro887 (accessed [today's date]).

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