Is GRIN1 p.Phe348= (c.1044C>T) pathogenic?

GRIN1 p.Phe348= (c.1044C>T) is classified Benign/Likely benign in GRIN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.214%, sas); Associated with Inborn genetic diseases.

What condition is associated with GRIN1 p.Phe348= (c.1044C>T)?

GRIN1 p.Phe348= (c.1044C>T) is associated with Inborn genetic diseases, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (ClinVar).

How common is GRIN1 p.Phe348= (c.1044C>T) in the general population?

GRIN1 p.Phe348= (c.1044C>T) is rare (popmax 0.214%, sas) (gnomAD).

GRIN1 p.Phe348=

c.1044C>T · rs143483243 · VCV385917

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.214%, sas)

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 -2.8	GERP -2.3
Overall
CADD	10.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% South Asian · 195/91,072 alleles

Filtering AF 0.189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.0178% 288/1,613,496 alleles · rare exomes 234/1,461,306 · genomes 54/152,190 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.214%	467
African / African-American	0.0733%	1,364
Remaining individualsnot grpmax-eligible	0.024%	4,166
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,008
European (non-Finnish)	0.00169%	58,997

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.Phe348=
Coding: c.1044C>T
MANE Select: NM_007327
dbSNP: rs143483243
Type: single nucleotide variant
Location: chr9:137158454 (GRCh38)
Structure: AlphaFold pLDDT 44.02
Residue 348: 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

Similar variants

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
GRIN1 p.Asp732Glu Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Gly618Arg 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-phe348 (accessed [today's date]).

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