Is GRIN2B p.Phe550Ser (c.1649T>C) pathogenic?

GRIN2B p.Phe550Ser (c.1649T>C) is classified Likely pathogenic in GRIN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-16). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GRIN2B p.Phe550Ser (c.1649T>C)?

GRIN2B p.Phe550Ser (c.1649T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2B p.Phe550Ser (c.1649T>C) in the general population?

GRIN2B p.Phe550Ser (c.1649T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2B p.Phe550Ser (c.1649T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

GRIN2B p.Phe550Ser

c.1649T>C · rs1555112021 · VCV522093

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 4% in GRIN2B
REVEL	0.72	pathogenic-leaning
SaProt	LLR -14.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 3,740 bp · p 9.8e-23 · regional, not allelic
Overall
CADD	33.0	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: GRIN2B
Protein: p.Phe550Ser
Coding: c.1649T>C
MANE Select: NM_000834
dbSNP: rs1555112021
Type: single nucleotide variant
Location: chr12:13615119 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 550: an α-helix

Full GRIN2B 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

Similar variants

GRIN2B p.Phe550Leu Uncertain significance ★ ⚠ same residue
GRIN2B p.Ala639Val Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Arg540His Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Arg696His Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Gly820Ala Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Gly820Arg Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Val686Met Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Ala1464Pro Uncertain significance ★★ ⚠ 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/grin2b-p-phe550ser (accessed [today's date]).

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