Is GRIN2A p.Pro32= (c.96C>A) pathogenic?

GRIN2A p.Pro32= (c.96C>A) is classified Likely benign in GRIN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.004%, afr); Associated with Landau-Kleffner syndrome.

What condition is associated with GRIN2A p.Pro32= (c.96C>A)?

GRIN2A p.Pro32= (c.96C>A) is associated with Landau-Kleffner syndrome (ClinVar).

How common is GRIN2A p.Pro32= (c.96C>A) in the general population?

GRIN2A p.Pro32= (c.96C>A) is very rare (popmax 0.004%, afr) (gnomAD).

How is Landau-Kleffner syndrome inherited?

Typically Autosomal dominant, Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

GRIN2A p.Pro32=

c.96C>A · rs776530090 · VCV2724590

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Landau-Kleffner syndrome

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 -1.8	GERP -3
Overall
CADD	8.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,610,758 alleles · very rare exomes 2/1,458,568 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,974
European (non-Finnish)	8.48e-05%	1,179,935

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.Pro32=
Coding: c.96C>A
MANE Select: NM_001134407
dbSNP: rs776530090
Type: single nucleotide variant
Location: chr16:10180316 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB

Full GRIN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Landau-Kleffner syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Landau-Kleffner syndrome (Orphanet):

Inheritance: Autosomal dominant, Unknown
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

GRIN2A p.Pro32Ser Likely benign ★ 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
GRIN2A c.415-2A>G 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-pro32 (accessed [today's date]).

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