Is GRIN2A p.Pro13= (c.39G>A) pathogenic?

GRIN2A p.Pro13= (c.39G>A) is classified Likely benign in GRIN2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-16). Very rare (popmax 0.000593%, nfe); Associated with Landau-Kleffner syndrome.

What condition is associated with GRIN2A p.Pro13= (c.39G>A)?

GRIN2A p.Pro13= (c.39G>A) is associated with Landau-Kleffner syndrome (ClinVar).

How common is GRIN2A p.Pro13= (c.39G>A) in the general population?

GRIN2A p.Pro13= (c.39G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

How is Landau-Kleffner syndrome inherited?

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

GRIN2A p.Pro13=

c.39G>A · rs776479105 · VCV1486510

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

Landau-Kleffner syndrome

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 0.58	GERP 0.36, phastCons 1
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,858 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000498% 8/1,607,986 alleles · very rare exomes 8/1,455,668 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00172%	58,160
European (non-Finnish)grpmax	0.000593%	168,551

Finnish 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: GRIN2A
Protein: p.Pro13=
Coding: c.39G>A
MANE Select: NM_001134407
dbSNP: rs776479105
Type: single nucleotide variant
Location: chr16:10180373 (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.Pro13Leu Likely benign ★★ same residue
GRIN2A p.Pro13Arg 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-pro13 (accessed [today's date]).

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