Is GRIN2B p.Pro952= (c.2856G>A) pathogenic?

GRIN2B p.Pro952= (c.2856G>A) is classified Likely benign in GRIN2B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). Very rare (popmax 0.0011%, sas); Associated with intellectual disability, autosomal dominant 6.

What condition is associated with GRIN2B p.Pro952= (c.2856G>A)?

GRIN2B p.Pro952= (c.2856G>A) is associated with intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

How common is GRIN2B p.Pro952= (c.2856G>A) in the general population?

GRIN2B p.Pro952= (c.2856G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

GRIN2B p.Pro952=

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.2856G>A · rs547507161 · VCV588908

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -3.2
Overall
CADD	8.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 0.000124% 2/1,614,144 alleles · very rare exomes 1/1,461,894 · genomes 1/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,180,020

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.Pro952=
Coding: c.2856G>A
MANE Select: NM_000834
dbSNP: rs547507161
Type: single nucleotide variant
Location: chr12:13564382 (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.Pro952Gln Likely pathogenic ★ ⚠ same residue
GRIN2B p.Pro952Ala Uncertain significance ★ ⚠ same residue
GRIN2B p.Pro952Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
GRIN2B p.Pro952Ser 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

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-pro952 (accessed [today's date]).

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