Is GRIN2D p.Ser285Phe (c.854C>T) pathogenic?

GRIN2D p.Ser285Phe (c.854C>T) is classified Likely benign in GRIN2D (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1925); Rare (popmax 0.148%, afr); Associated with Inborn genetic diseases.

What condition is associated with GRIN2D p.Ser285Phe (c.854C>T)?

GRIN2D p.Ser285Phe (c.854C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2D p.Ser285Phe (c.854C>T) in the general population?

GRIN2D p.Ser285Phe (c.854C>T) is rare (popmax 0.148%, afr) (gnomAD).

What do computational predictors say about GRIN2D p.Ser285Phe (c.854C>T)?

AlphaMissense predicts likely benign (score 0.1925) — an in-silico prediction, not a clinical call.

GRIN2D p.Ser285Phe

c.854C>T · rs185295623 · VCV730629

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1925 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1925	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 5.9e-06 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.148% African / African-American · 110/74,158 alleles

Filtering AF 0.126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.117%

Overall 0.00716% 113/1,577,790 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.148%	674
Remaining individualsnot grpmax-eligible	0.00492%	20,309

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: GRIN2D
Protein: p.Ser285Phe
Coding: c.854C>T
MANE Select: NM_000836
dbSNP: rs185295623
Type: single nucleotide variant
Location: chr19:48405122 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB
Residue 285: a disulfide bond

Full GRIN2D 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

GRIN2D p.Ala1032Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1135Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1208Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1244Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1256Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1310Gly Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala149Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala249Thr 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-ser285phe (accessed [today's date]).

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