Is GRIN1 p.Ser85= (c.255C>T) pathogenic?

GRIN1 p.Ser85= (c.255C>T) is classified Conflicting classifications of pathogenicity in GRIN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-12). Very rare (popmax 0.005%, amr); Associated with neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant.

How common is GRIN1 p.Ser85= (c.255C>T) in the general population?

GRIN1 p.Ser85= (c.255C>T) is very rare (popmax 0.005%, amr) (gnomAD).

GRIN1 p.Ser85=

Q: What condition is associated with GRIN1 p.Ser85= (c.255C>T)?

GRIN1 p.Ser85= (c.255C>T) is associated with neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (ClinVar).

c.255C>T · rs797045605 · VCV211110

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.94 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 1
Overall
CADD	15.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,012 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,066 alleles · very rare exomes 1/1,460,872 · genomes 2/152,194 · 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: GRIN1
Protein: p.Ser85=
Coding: c.255C>T
MANE Select: NM_007327
dbSNP: rs797045605
Type: single nucleotide variant
Location: chr9:137139741 (GRCh38)
Structure: AlphaFold pLDDT 44.02
Residue 85: the 'disordered' region

Full GRIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRIN1 p.Arg659Gln Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg659Trp Pathogenic ★★ same condition
GRIN1 p.Arg794Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
GRIN1 p.Arg844Cys Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg844Leu Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Asp227His Likely pathogenic ★★ same condition
GRIN1 p.Asp732Glu Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Gly618Arg 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/grin1-p-ser85 (accessed [today's date]).

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