Is GRID1 p.Pro120Gln (c.359C>A) pathogenic?

GRID1 p.Pro120Gln (c.359C>A) is classified Uncertain significance in GRID1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-13). AlphaMissense: likely benign (0.0845); Ultra-rare (popmax 0.0825%, mid); Associated with GRID1-associated neurodevelopmental disorder.

What condition is associated with GRID1 p.Pro120Gln (c.359C>A)?

GRID1 p.Pro120Gln (c.359C>A) is associated with GRID1-associated neurodevelopmental disorder (ClinVar).

How common is GRID1 p.Pro120Gln (c.359C>A) in the general population?

GRID1 p.Pro120Gln (c.359C>A) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about GRID1 p.Pro120Gln (c.359C>A)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

GRID1 p.Pro120Gln

c.359C>A · rs143664937 · VCV2502415

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GRID1-associated neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.18	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 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 510 kb · p 5.7e-07 · regional, not allelic
Overall
CADD	23.3	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 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.043%

Overall 0.014% 226/1,614,216 alleles · ultra-rare exomes 211/1,461,874 · genomes 15/152,342 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
South Asian	0.0604%	1,656
Admixed American	0.0217%	4,618
European (non-Finnish)	0.0124%	8,083
Remaining individualsnot grpmax-eligible	0.008%	12,502
African / African-American	0.00266%	37,530

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.Pro120Gln
Coding: c.359C>A
MANE Select: NM_017551
dbSNP: rs143664937
Type: single nucleotide variant
Location: chr10:86206525 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 3 PDB
Residue 120: 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.Arg384Gln Uncertain significance ★★ ⚠ same condition
GRID1 p.Asp307Asn Uncertain significance ★★ ⚠ same condition
GRID1 p.Gly716Arg Uncertain significance ★★ ⚠ same condition
GRID1 p.Thr604Ile Uncertain significance ★★ ⚠ same condition
GRID1 p.Val450Met 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-pro120gln (accessed [today's date]).

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