Is GRID1 p.Asp684His (c.2050G>C) pathogenic?

GRID1 p.Asp684His (c.2050G>C) is classified Uncertain significance in GRID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely pathogenic (0.5817); Absent from gnomAD v4.1; Associated with GRID1-associated neurodevelopmental disorder.

What condition is associated with GRID1 p.Asp684His (c.2050G>C)?

GRID1 p.Asp684His (c.2050G>C) is associated with GRID1-associated neurodevelopmental disorder (ClinVar).

How common is GRID1 p.Asp684His (c.2050G>C) in the general population?

GRID1 p.Asp684His (c.2050G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRID1 p.Asp684His (c.2050G>C)?

AlphaMissense predicts likely pathogenic (score 0.5817) — an in-silico prediction, not a clinical call.

GRID1 p.Asp684His

c.2050G>C · rs2492773302 · VCV2502405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5817 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GRID1-associated neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.5817	likely pathogenic
REVEL	0.318	indeterminate
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 254 kb · p 0.00028 · regional, not allelic
Overall
CADD	28.4	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

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: GRID1
Protein: p.Asp684His
Coding: c.2050G>C
MANE Select: NM_017551
dbSNP: rs2492773302
Type: single nucleotide variant
Location: chr10:85647345 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 3 PDB

Full GRID1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GRID1-associated neurodevelopmental disorder

Similar variants

GRID1 p.Ala127Thr Uncertain significance ★★ ⚠ same condition
GRID1 p.Ala603Asp Uncertain significance ★★ ⚠ same condition
GRID1 p.Arg221Gln Uncertain significance ★★ ⚠ same condition
GRID1 p.Arg384Gln Uncertain significance ★★ ⚠ same condition
GRID1 p.Asp307Asn Uncertain significance ★★ ⚠ same condition
GRID1 p.Gly716Arg Uncertain significance ★★ ⚠ same condition
GRID1 p.Pro120Gln Uncertain significance ★★ ⚠ same condition
GRID1 p.Thr604Ile 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/grid1-p-asp684his (accessed [today's date]).

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