Is GRID1 p.Pro429Thr (c.1285C>A) pathogenic?

GRID1 p.Pro429Thr (c.1285C>A) is classified Uncertain significance in GRID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.0805); Ultra-rare (popmax 0.0242%, sas); Associated with GRID1-associated neurodevelopmental disorder.

What condition is associated with GRID1 p.Pro429Thr (c.1285C>A)?

GRID1 p.Pro429Thr (c.1285C>A) is associated with GRID1-associated neurodevelopmental disorder (ClinVar).

How common is GRID1 p.Pro429Thr (c.1285C>A) in the general population?

GRID1 p.Pro429Thr (c.1285C>A) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about GRID1 p.Pro429Thr (c.1285C>A)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

GRID1 p.Pro429Thr

c.1285C>A · rs772108088 · VCV2502398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GRID1-associated neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	donor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 254 kb · p 0.00028 · regional, not allelic
Overall
CADD	23.6	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 0.0242% South Asian · 22/90,974 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00149% 24/1,612,892 alleles · ultra-rare exomes 24/1,460,694 · genomes 0/152,198 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,135
Remaining individualsnot grpmax-eligible	0.0032%	31,227

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.Pro429Thr
Coding: c.1285C>A
MANE Select: NM_017551
dbSNP: rs772108088
Type: single nucleotide variant
Location: chr10:85729563 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 3 PDB
Residue 429: 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.Pro429Arg Uncertain significance ★ ⚠ same residue
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

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-pro429thr (accessed [today's date]).

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