Is GRIN2B p.Pro952Ser (c.2854C>T) pathogenic?

GRIN2B p.Pro952Ser (c.2854C>T) is classified Benign in GRIN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0679); Very rare (popmax 6.19e-05%); Associated with developmental and epileptic encephalopathy, 27.

What condition is associated with GRIN2B p.Pro952Ser (c.2854C>T)?

GRIN2B p.Pro952Ser (c.2854C>T) is associated with developmental and epileptic encephalopathy, 27, intellectual disability, autosomal dominant 6 (ClinVar).

How common is GRIN2B p.Pro952Ser (c.2854C>T) in the general population?

GRIN2B p.Pro952Ser (c.2854C>T) is very rare (popmax 6.19e-05%) (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

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

What do computational predictors say about GRIN2B p.Pro952Ser (c.2854C>T)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

GRIN2B p.Pro952Ser

c.2854C>T · rs1565454641 · VCV572311

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.19e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 27

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -4.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.65, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 419 bp · p 0.00052 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.19e-05%

Overall 6.19e-05% 1/1,614,234 alleles · very rare exomes 1/1,461,894 · genomes 0/152,340 · joint denominator

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.Pro952Ser
Coding: c.2854C>T
MANE Select: NM_000834
dbSNP: rs1565454641
Type: single nucleotide variant
Location: chr12:13564384 (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

developmental and epileptic encephalopathy, 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, autosomal dominant 6

For Infantile epileptic spasms syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant

Similar variants

GRIN2B p.Pro952= Likely benign ★★ same residue
GRIN2B p.Pro952Gln Likely pathogenic ★ ⚠ same residue
GRIN2B p.Pro952Ala Uncertain significance ★ ⚠ same residue
GRIN2B p.Pro952Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro952ser (accessed [today's date]).

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