Is GRID1 p.Lys199Arg (c.596A>G) pathogenic?

GRID1 p.Lys199Arg (c.596A>G) is classified Uncertain significance in GRID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.0604); Absent from gnomAD v4.1; Associated with GRID1-associated neurodevelopmental disorder.

What condition is associated with GRID1 p.Lys199Arg (c.596A>G)?

GRID1 p.Lys199Arg (c.596A>G) is associated with GRID1-associated neurodevelopmental disorder (ClinVar).

How common is GRID1 p.Lys199Arg (c.596A>G) in the general population?

GRID1 p.Lys199Arg (c.596A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRID1 p.Lys199Arg (c.596A>G)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

GRID1 p.Lys199Arg

c.596A>G · rs1349977226 · VCV2502391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

GRID1-associated neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 510 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	19.87	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: GRID1
Protein: p.Lys199Arg
Coding: c.596A>G
MANE Select: NM_017551
dbSNP: rs1349977226
Type: single nucleotide variant
Location: chr10:86138949 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 3 PDB
Residue 199: the 'interaction with cbln1' region

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-lys199arg (accessed [today's date]).

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