Is GRIN2D p.Ala855Ser (c.2563G>T) pathogenic?

GRIN2D p.Ala855Ser (c.2563G>T) is classified Uncertain significance in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-11). AlphaMissense: likely pathogenic (0.6028); Absent from gnomAD v4.1; Associated with GRIN2D-related disorder.

What condition is associated with GRIN2D p.Ala855Ser (c.2563G>T)?

GRIN2D p.Ala855Ser (c.2563G>T) is associated with GRIN2D-related disorder (ClinVar).

How common is GRIN2D p.Ala855Ser (c.2563G>T) in the general population?

GRIN2D p.Ala855Ser (c.2563G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2D p.Ala855Ser (c.2563G>T)?

AlphaMissense predicts likely pathogenic (score 0.6028) — an in-silico prediction, not a clinical call.

GRIN2D p.Ala855Ser

c.2563G>T · rs2513691157 · VCV2630182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6028 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

GRIN2D-related disorder

Computational evidence

Protein change
AlphaMissense	0.6028	likely pathogenic
REVEL	0.396	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 23 kb · p 8.9e-16 · regional, not allelic
Overall
CADD	31.0	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: GRIN2D
Protein: p.Ala855Ser
Coding: c.2563G>T
MANE Select: NM_000836
dbSNP: rs2513691157
Type: single nucleotide variant
Location: chr19:48442272 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB
Residue 855: an α-helix

Full GRIN2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GRIN2D-related disorder

Similar variants

GRIN2D p.Ala855= Likely benign ★ same residue
GRIN2D p.Ala666Val Conflicting classifications of pathogenicity ★ ⚠ same condition
GRIN2D p.Pro1171Leu Uncertain significance ★ ⚠ same condition
GRIN2D p.Pro1213Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
GRIN2D p.Ser1173Thr Uncertain significance ★ ⚠ same condition
GRIN2D p.Ser1271Trp Uncertain significance ★ ⚠ same condition
GRIN2D p.Thr1288Ser Uncertain significance ★ ⚠ same condition
GRIN2D p.Gln704His 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/grin2d-p-ala855ser (accessed [today's date]).

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