Is GRIN2C p.Phe577Val (c.1729T>G) pathogenic?

GRIN2C p.Phe577Val (c.1729T>G) is classified Uncertain significance in GRIN2C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.148); Absent from gnomAD v4.1.

How common is GRIN2C p.Phe577Val (c.1729T>G) in the general population?

GRIN2C p.Phe577Val (c.1729T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2C p.Phe577Val (c.1729T>G)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

GRIN2C p.Phe577Val

c.1729T>G · VCV4833229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.32	donor gain · deltas
Constraint at this position
Conservation	phyloP 6.8	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,960 bp · p 1.4e-06 · regional, not allelic
Overall
CADD	26.4	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: GRIN2C
Protein: p.Phe577Val
Coding: c.1729T>G
MANE Select: NM_000835
Type: single nucleotide variant
Location: chr17:74847894 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 6 PDB
Residue 577: 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-phe577val (accessed [today's date]).

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