Is GRIN2D p.Ala926Val (c.2777C>T) pathogenic?

GRIN2D p.Ala926Val (c.2777C>T) is classified Uncertain significance in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely benign (0.0804); No allele count reported in gnomAD v4.1 (AN 1,156,342); Associated with developmental and epileptic encephalopathy, 46.

What condition is associated with GRIN2D p.Ala926Val (c.2777C>T)?

GRIN2D p.Ala926Val (c.2777C>T) is associated with developmental and epileptic encephalopathy, 46 (ClinVar).

How common is GRIN2D p.Ala926Val (c.2777C>T) in the general population?

GRIN2D p.Ala926Val (c.2777C>T) is no allele count reported in gnomAD v4.1 (AN 1,156,342) (gnomAD).

What do computational predictors say about GRIN2D p.Ala926Val (c.2777C>T)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

GRIN2D p.Ala926Val

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

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

c.2777C>T · rs2513691816 · VCV2432306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,156,342)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 46

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -8.40	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 3.2	GERP 0.88, phastCons 0.17
Regional constraint	o/e 1.10	unconstrained · MANE · 1,409 bp · p 0.013 · regional, not allelic
Overall
CADD	16.83	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

No allele count reported in gnomAD v4.1 (AN 1,156,342). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GRIN2D
Protein: p.Ala926Val
Coding: c.2777C>T
MANE Select: NM_000836
dbSNP: rs2513691816
Type: single nucleotide variant
Location: chr19:48442703 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB
Residue 926: the 'disordered' region; a UniProt-annotated variant site (found in a patient with autism spectrum disorder; uncertain significance)

Full GRIN2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 46 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

GRIN2D p.Met681Val Pathogenic/Likely pathogenic ★★ same condition
GRIN2D p.Val667Ile Pathogenic/Likely pathogenic ★★ same condition
GRIN2D p.Ala1085Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1310Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala149Gly Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala280Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Arg1181Pro Uncertain significance ★★ ⚠ same condition
GRIN2D p.Arg1223Gln Uncertain significance ★★ ⚠ 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/grin2d-p-ala926val (accessed [today's date]).

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