Is GRIN2A p.Ser245Phe (c.734C>T) pathogenic?

GRIN2A p.Ser245Phe (c.734C>T) is classified Uncertain significance in GRIN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.395); Absent from gnomAD v4.1.

How common is GRIN2A p.Ser245Phe (c.734C>T) in the general population?

GRIN2A p.Ser245Phe (c.734C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2A p.Ser245Phe (c.734C>T)?

AlphaMissense predicts ambiguous (score 0.395) — an in-silico prediction, not a clinical call.

GRIN2A p.Ser245Phe

c.734C>T · VCV3898420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.395 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.395	ambiguous
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -9.65	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 339 kb · p 0.00058 · regional, not allelic
Overall
CADD	28.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRIN2A
Protein: p.Ser245Phe
Coding: c.734C>T
MANE Select: NM_001134407
Type: single nucleotide variant
Location: chr16:9938232 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 245: a turn; 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

Similar variants

GRIN2A p.Ser245Cys Uncertain significance ★★ ⚠ same residue
GRIN2A p.Ser245Thr Uncertain significance ★ ⚠ same residue
GRIN2A p.Ser245= Likely benign ★ same residue
GRIN2A c.1007+1G>A Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.1007+1G>T Pathogenic ★★ same type
GRIN2A c.1123-2A>G Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.1497+1G>T Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.2007+1G>T Likely pathogenic ★★ same type

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-ser245phe (accessed [today's date]).

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