Is GRIN2B p.Asp138= (c.414T>C) pathogenic?

GRIN2B p.Asp138= (c.414T>C) is classified Likely benign in GRIN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-12). Very rare (popmax 0.000344%, nfe); Associated with intellectual disability, autosomal dominant 6.

What condition is associated with GRIN2B p.Asp138= (c.414T>C)?

GRIN2B p.Asp138= (c.414T>C) is associated with intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

How common is GRIN2B p.Asp138= (c.414T>C) in the general population?

GRIN2B p.Asp138= (c.414T>C) is very rare (popmax 0.000344%, nfe) (gnomAD).

GRIN2B p.Asp138=

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.414T>C · rs1156646657 · VCV2938058

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000344%, 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	all four deltas below 0.2 · A>T here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.57	GERP -0.94, phastCons 0.86
Overall
CADD	8.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000344% European (non-Finnish) · 4/1,163,336 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000251% 4/1,595,824 alleles · very rare exomes 4/1,443,462 · genomes 0/152,362 · 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.Asp138=
Coding: c.414T>C
MANE Select: NM_000834
dbSNP: rs1156646657
Type: single nucleotide variant
Location: chr12:13753913 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 138: an α-helix

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-asp138 (accessed [today's date]).

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