Is GRIN2B p.Ser63= (c.189C>T) pathogenic?

GRIN2B p.Ser63= (c.189C>T) is classified Likely benign in GRIN2B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). Very rare (popmax 0.00534%, afr); Associated with developmental and epileptic encephalopathy, 27.

What condition is associated with GRIN2B p.Ser63= (c.189C>T)?

GRIN2B p.Ser63= (c.189C>T) is associated with developmental and epileptic encephalopathy, 27, intellectual disability, autosomal dominant 6 (ClinVar).

How common is GRIN2B p.Ser63= (c.189C>T) in the general population?

GRIN2B p.Ser63= (c.189C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

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

GRIN2B p.Ser63=

c.189C>T · rs199707487 · VCV307753

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

developmental and epileptic encephalopathy, 27

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 -8.6	GERP -3.7
Overall
CADD	1.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,900 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00304% 49/1,613,878 alleles · very rare exomes 40/1,461,776 · genomes 9/152,102 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,498
African / African-Americangrpmax	0.00534%	18,725
European (non-Finnish)	0.00322%	31,051
Admixed American	0.00167%	59,998
South Asian	0.0011%	91,072

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.Ser63=
Coding: c.189C>T
MANE Select: NM_000834
dbSNP: rs199707487
Type: single nucleotide variant
Location: chr12:13866020 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 63: a β-strand

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.Ser63Pro Uncertain significance ★ ⚠ same residue
GRIN2B p.Ser63Phe 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

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-ser63 (accessed [today's date]).

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