Is GRIN2C p.Met826Val (c.2476A>G) pathogenic?

GRIN2C p.Met826Val (c.2476A>G) is classified Uncertain significance in GRIN2C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: ambiguous (0.4108); Very rare (popmax 0.004%, afr).

How common is GRIN2C p.Met826Val (c.2476A>G) in the general population?

GRIN2C p.Met826Val (c.2476A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about GRIN2C p.Met826Val (c.2476A>G)?

AlphaMissense predicts ambiguous (score 0.4108) — an in-silico prediction, not a clinical call.

GRIN2C p.Met826Val

c.2476A>G · VCV4267055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
AlphaMissense	0.4108	ambiguous
REVEL	0.434	indeterminate
SaProt	LLR -9.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,960 bp · p 1.4e-06 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.004% African / African-American · 3/74,912 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,082 alleles · very rare exomes 2/1,461,886 · genomes 1/152,196 · 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: GRIN2C
Protein: p.Met826Val
Coding: c.2476A>G
MANE Select: NM_000835
Type: single nucleotide variant
Location: chr17:74844383 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 6 PDB
Residue 826: a UniProt-annotated variant site (found in a patient with autism spectrum disorder; uncertain significance)

Full GRIN2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRIN2C p.Ala8Thr Likely benign ★★ same type
GRIN2C p.Ala999= Likely benign ★★ same type
GRIN2C p.Arg401Gln Benign ★★ same type
GRIN2C p.Arg435= Benign ★★ same type
GRIN2C p.Ile519= Benign/Likely benign ★★ same type
GRIN2C p.Leu65Phe Likely benign ★★ same type
GRIN2C p.Thr1196Ile Benign ★★ same type
GRIN2C p.Val191Ala Likely benign ★★ same type

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/grin2c-p-met826val (accessed [today's date]).

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