Is GRID1 p.Arg384Gln (c.1151G>A) pathogenic?

GRID1 p.Arg384Gln (c.1151G>A) is classified Uncertain significance in GRID1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0752); Ultra-rare (popmax 0.0345%, nfe); Associated with GRID1-associated neurodevelopmental disorder.

What condition is associated with GRID1 p.Arg384Gln (c.1151G>A)?

GRID1 p.Arg384Gln (c.1151G>A) is associated with GRID1-associated neurodevelopmental disorder (ClinVar).

How common is GRID1 p.Arg384Gln (c.1151G>A) in the general population?

GRID1 p.Arg384Gln (c.1151G>A) is ultra-rare (popmax 0.0345%, nfe) (gnomAD).

What do computational predictors say about GRID1 p.Arg384Gln (c.1151G>A)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

GRID1 p.Arg384Gln

c.1151G>A · rs118168995 · VCV2341592

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0345%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GRID1-associated neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -6.11	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 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 254 kb · p 0.00028 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.0345% European (non-Finnish) · 407/1,179,694 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0306%

Overall 0.0289% 466/1,613,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0608%	1,644
European (non-Finnish)grpmax	0.0345%	2,899
Finnishnot grpmax-eligible	0.0172%	5,820
Middle Eastern	0.0165%	6,060
Admixed American	0.01%	10,004
African / African-American	0.004%	25,010

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GRID1
Protein: p.Arg384Gln
Coding: c.1151G>A
MANE Select: NM_017551
dbSNP: rs118168995
Type: single nucleotide variant
Location: chr10:85854578 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 3 PDB
Residue 384: 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

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GRID1 p.Gly716Arg Uncertain significance ★★ ⚠ same condition
GRID1 p.Pro120Gln Uncertain significance ★★ ⚠ same condition
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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-arg384gln (accessed [today's date]).

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