Is GRIN1 p.Pro263= (c.789A>G) pathogenic?

GRIN1 p.Pro263= (c.789A>G) is classified Benign in GRIN1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 32.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

GRIN1 p.Pro263=

Q: What condition is associated with GRIN1 p.Pro263= (c.789A>G)?

GRIN1 p.Pro263= (c.789A>G) is associated with Inborn genetic diseases, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (ClinVar).

Q: How common is GRIN1 p.Pro263= (c.789A>G) in the general population?

GRIN1 p.Pro263= (c.789A>G) is common (popmax 32.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.789A>G · rs6293 · VCV129182

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 32.8%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -2.2
Overall
CADD	2.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.8% European (non-Finnish) · 383,384/1,169,736 alleles

Filtering AF 32.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.7%

Overall 29.6% 470,913/1,592,168 alleles · common exomes 435,155/1,439,878 · genomes 35,758/152,290 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	43.9%	2
Finnishnot grpmax-eligible	41%	2
European (non-Finnish)grpmax	32.8%	3
Middle Eastern	27.9%	4
Remaining individualsnot grpmax-eligible	26.6%	4
Ashkenazi Jewishnot grpmax-eligible	26.2%	4
South Asian	22.8%	4
Admixed American	20.6%	5
African / African-American	6.13%	16
East Asian	0.158%	633

Amish 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: GRIN1
Protein: p.Pro263=
Coding: c.789A>G
MANE Select: NM_007327
dbSNP: rs6293
Type: single nucleotide variant
Location: chr9:137156786 (GRCh38)
Structure: AlphaFold pLDDT 44.02
Residue 263: the 'disordered' region

Full GRIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive

Similar variants

GRIN1 p.Pro263Ser Uncertain significance ★ ⚠ same residue
GRIN1 p.Pro263Arg Uncertain significance ★ same residue
GRIN1 p.Arg659Gln Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg659Trp Pathogenic ★★ same condition
GRIN1 p.Arg794Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
GRIN1 p.Arg844Cys Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg844Leu Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Asp227His Likely pathogenic ★★ 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/grin1-p-pro263 (accessed [today's date]).

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