Is GRIN2A p.Pro31Ser (c.91C>T) pathogenic?

GRIN2A p.Pro31Ser (c.91C>T) is classified Conflicting classifications of pathogenicity in GRIN2A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-30). AlphaMissense: likely benign (0.0818); Very rare (popmax 0.00934%, afr); Associated with Inborn genetic diseases.

What condition is associated with GRIN2A p.Pro31Ser (c.91C>T)?

GRIN2A p.Pro31Ser (c.91C>T) is associated with Inborn genetic diseases, Landau-Kleffner syndrome (ClinVar).

How common is GRIN2A p.Pro31Ser (c.91C>T) in the general population?

GRIN2A p.Pro31Ser (c.91C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about GRIN2A p.Pro31Ser (c.91C>T)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

GRIN2A p.Pro31Ser

c.91C>T · rs199942034 · VCV983352

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -3, phastCons 0.42
Regional constraint	o/e 0.83	unconstrained · MANE · 371 bp · p 0.025 · regional, not allelic
Overall
CADD	10.04	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,914 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000745% 12/1,610,404 alleles · very rare exomes 9/1,458,224 · genomes 3/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,702
Remaining individualsnot grpmax-eligible	0.0064%	15,615
European (non-Finnish)	8.47e-05%	1,179,944

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.Pro31Ser
Coding: c.91C>T
MANE Select: NM_001134407
dbSNP: rs199942034
Type: single nucleotide variant
Location: chr16:10180321 (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

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

Also linked: Landau-Kleffner syndrome

Similar variants

GRIN2A p.Pro31Arg Uncertain significance ★★ ⚠ same residue
GRIN2A p.Pro31Leu Uncertain significance ★ ⚠ same residue
GRIN2A p.Pro31Thr Uncertain significance ★ ⚠ same residue
GRIN2A p.Pro31= Likely benign ★ same residue
GRIN2A p.Pro31fs Likely pathogenic ★ 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

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-pro31ser (accessed [today's date]).

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