Is GRID2 p.Trp855Cys (c.2565G>C) pathogenic?

GRID2 p.Trp855Cys (c.2565G>C) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-09). AlphaMissense: likely pathogenic (0.8079); Ultra-rare (popmax 0.02%, amr).

How common is GRID2 p.Trp855Cys (c.2565G>C) in the general population?

GRID2 p.Trp855Cys (c.2565G>C) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about GRID2 p.Trp855Cys (c.2565G>C)?

AlphaMissense predicts likely pathogenic (score 0.8079) — an in-silico prediction, not a clinical call.

GRID2 p.Trp855Cys

c.2565G>C · VCV4811729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8079	likely pathogenic
REVEL	0.554	indeterminate
SaProt	LLR -11.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 548 kb · p 0.0047 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,996 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000744% 12/1,613,968 alleles · ultra-rare exomes 12/1,461,698 · genomes 0/152,270 · joint denominator

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: GRID2
Protein: p.Trp855Cys
Coding: c.2565G>C
MANE Select: NM_001510
Type: single nucleotide variant
Location: chr4:93769414 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB

Full GRID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRID2 p.Trp855Ter Likely pathogenic ★ same residue
GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same type
GRID2 p.Thr649Ala Pathogenic/Likely pathogenic ★★ same type
GRID2 p.Ala196Glu Uncertain significance ★★ ⚠ same type
GRID2 p.Ala21Val Uncertain significance ★★ ⚠ same type
GRID2 p.Ala574Ser Uncertain significance ★★ ⚠ same type
GRID2 p.Arg229Gln Uncertain significance ★★ ⚠ same type
GRID2 p.Arg297Gln Uncertain significance ★★ ⚠ 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/grid2-p-trp855cys (accessed [today's date]).

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