Is GRIN2A p.Val417= (c.1251C>T) pathogenic?

GRIN2A p.Val417= (c.1251C>T) is classified Benign/Likely benign in GRIN2A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Rare (popmax 0.523%, afr); Associated with Inborn genetic diseases.

What condition is associated with GRIN2A p.Val417= (c.1251C>T)?

GRIN2A p.Val417= (c.1251C>T) is associated with Inborn genetic diseases, Landau-Kleffner syndrome (ClinVar).

How common is GRIN2A p.Val417= (c.1251C>T) in the general population?

GRIN2A p.Val417= (c.1251C>T) is rare (popmax 0.523%, afr) (gnomAD).

GRIN2A p.Val417=

c.1251C>T · rs139329447 · VCV137508

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.523%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP 2, phastCons 1
Overall
CADD	9.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.523% African / African-American · 392/75,012 alleles

Filtering AF 0.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.463%

Overall 0.0317% 512/1,614,022 alleles · rare exomes 271/1,461,790 · genomes 241/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.523%	191
Middle Eastern	0.0825%	1,212
Admixed American	0.0716%	1,396
Remaining individualsnot grpmax-eligible	0.0528%	1,894
European (non-Finnish)	0.00322%	31,051
South Asian	0.0011%	91,078

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: GRIN2A
Protein: p.Val417=
Coding: c.1251C>T
MANE Select: NM_001134407
dbSNP: rs139329447
Type: single nucleotide variant
Location: chr16:9849833 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 417: a β-strand; a UniProt-annotated variant site (found in schizophrenia; uncertain significance; loss of function in ion transmembrane transport; the channel is not activated by glutamate)

Full GRIN2A 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: Landau-Kleffner syndrome

Similar variants

GRIN2A p.Val417Ile Uncertain significance ★ ⚠ same residue
GRIN2A p.Val417Phe Uncertain significance ★ ⚠ same residue
GRIN2A c.1007+1G>A Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.1007+1G>T Pathogenic ★★ same condition
GRIN2A c.1123-2A>G Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.1497+1G>T Pathogenic/Likely pathogenic ★★ same condition
GRIN2A c.2007+1G>T Likely pathogenic ★★ same condition
GRIN2A c.2168+1G>C Pathogenic/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/grin2a-p-val417 (accessed [today's date]).

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