Is GRIN2B p.Asp381Glu (c.1143C>G) pathogenic?

GRIN2B p.Asp381Glu (c.1143C>G) is classified Uncertain significance in GRIN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1024); Absent from gnomAD v4.1.

How common is GRIN2B p.Asp381Glu (c.1143C>G) in the general population?

GRIN2B p.Asp381Glu (c.1143C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2B p.Asp381Glu (c.1143C>G)?

AlphaMissense predicts likely benign (score 0.1024) — an in-silico prediction, not a clinical call.

GRIN2B p.Asp381Glu

c.1143C>G · VCV3777365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1024 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1024	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -6.81	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 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 249 kb · p 1.8e-30 · regional, not allelic
Overall
CADD	18.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRIN2B
Protein: p.Asp381Glu
Coding: c.1143C>G
MANE Select: NM_000834
Type: single nucleotide variant
Location: chr12:13616640 (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

Similar variants

GRIN2B p.Asp381= Likely benign ★ same residue
GRIN2B c.2172-2A>G Pathogenic ★★ same type
GRIN2B p.Ala639Val Pathogenic/Likely pathogenic ★★ same type
GRIN2B p.Ala644Asp Pathogenic ★★ same type
GRIN2B p.Ala734Val Likely pathogenic ★★ same type
GRIN2B p.Ala819Thr Pathogenic/Likely pathogenic ★★ same type
GRIN2B p.Arg1111His Pathogenic/Likely pathogenic ★★ ⚠ same type
GRIN2B p.Arg393Ter Pathogenic/Likely pathogenic ★★ same type

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-asp381glu (accessed [today's date]).

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