Is GRIN2D p.Ser573Phe (c.1718C>T) pathogenic?

GRIN2D p.Ser573Phe (c.1718C>T) is classified Pathogenic in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-01). AlphaMissense: likely pathogenic (0.9989); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 46.

What condition is associated with GRIN2D p.Ser573Phe (c.1718C>T)?

GRIN2D p.Ser573Phe (c.1718C>T) is associated with developmental and epileptic encephalopathy, 46 (ClinVar).

How common is GRIN2D p.Ser573Phe (c.1718C>T) in the general population?

GRIN2D p.Ser573Phe (c.1718C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2D p.Ser573Phe (c.1718C>T)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

GRIN2D p.Ser573Phe

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1718C>T · rs2147452753 · VCV1325736

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 46

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic ✓ concordant with ClinVar · top 8% in GRIN2D
REVEL	0.532	indeterminate
SaProt	LLR -14.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.60 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 5,266 bp · p 6.3e-14 · 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: GRIN2D
Protein: p.Ser573Phe
Coding: c.1718C>T
MANE Select: NM_000836
dbSNP: rs2147452753
Type: single nucleotide variant
Location: chr19:48416138 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB

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

Disease context

developmental and epileptic encephalopathy, 46 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

GRIN2D p.Met681Val Pathogenic/Likely pathogenic ★★ same condition
GRIN2D p.Val667Ile Pathogenic/Likely pathogenic ★★ same condition
GRIN2D p.Ala1085Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1310Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala149Gly Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala280Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Arg1181Pro Uncertain significance ★★ ⚠ same condition
GRIN2D p.Arg1223Gln 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-ser573phe (accessed [today's date]).

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