Is GRIN2B p.Ser617= (c.1851C>T) pathogenic?

GRIN2B p.Ser617= (c.1851C>T) is classified Conflicting classifications of pathogenicity in GRIN2B (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-03). Rare (popmax 0.183%, sas); Associated with Inborn genetic diseases.

What condition is associated with GRIN2B p.Ser617= (c.1851C>T)?

GRIN2B p.Ser617= (c.1851C>T) is associated with Inborn genetic diseases, intellectual disability, autosomal dominant 6, developmental and epileptic encephalopathy, 27 (ClinVar).

How common is GRIN2B p.Ser617= (c.1851C>T) in the general population?

GRIN2B p.Ser617= (c.1851C>T) is rare (popmax 0.183%, sas) (gnomAD).

GRIN2B p.Ser617=

c.1851C>T · rs147373250 · VCV211121

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.183%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	acceptor gain · deltas
Pangolin	Δ0.32	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.9	GERP 0.98, phastCons 1
Overall
CADD	18.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% South Asian · 167/91,072 alleles

Filtering AF 0.161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.152%

Overall 0.0769% 1,242/1,614,048 alleles · rare exomes 1,168/1,461,820 · genomes 74/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.183%	545
Ashkenazi Jewishnot grpmax-eligible	0.176%	569
Remaining individualsnot grpmax-eligible	0.0832%	1,202
European (non-Finnish)	0.0793%	1,261
Finnishnot grpmax-eligible	0.0281%	3,558
Middle Eastern	0.0165%	6,060
African / African-American	0.0133%	7,502
Admixed American	0.00667%	15,004
East Asian	0.00446%	22,437

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: GRIN2B
Protein: p.Ser617=
Coding: c.1851C>T
MANE Select: NM_000834
dbSNP: rs147373250
Type: single nucleotide variant
Location: chr12:13608762 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.66 · 36 PDB
Residue 617: the 'pore-forming' region

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

Also linked: intellectual disability, autosomal dominant 6 developmental and epileptic encephalopathy, 27

Similar variants

GRIN2B p.Ser617Thr Pathogenic ★ ⚠ same residue
GRIN2B c.2172-2A>G Pathogenic ★★ same condition
GRIN2B p.Ala639Val Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Ala644Asp Pathogenic ★★ same condition
GRIN2B p.Ala734Val Likely pathogenic ★★ same condition
GRIN2B p.Ala819Thr Pathogenic/Likely pathogenic ★★ same condition
GRIN2B p.Arg1111His Pathogenic/Likely pathogenic ★★ ⚠ same condition
GRIN2B p.Arg393Ter Pathogenic/Likely pathogenic ★★ 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-ser617 (accessed [today's date]).

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