Is GRIA4 p.Ala554Val (c.1661C>T) pathogenic?

GRIA4 p.Ala554Val (c.1661C>T) is classified Uncertain significance in GRIA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1.

How common is GRIA4 p.Ala554Val (c.1661C>T) in the general population?

GRIA4 p.Ala554Val (c.1661C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIA4 p.Ala554Val (c.1661C>T)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

GRIA4 p.Ala554Val

c.1661C>T · rs1947655442 · VCV2692490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic · top 10% in GRIA4
REVEL	0.433	indeterminate
SaProt	LLR -12.72	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 6.6, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 64 kb · p 2.8e-28 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: GRIA4
Protein: p.Ala554Val
Coding: c.1661C>T
MANE Select: NM_000829
dbSNP: rs1947655442
Type: single nucleotide variant
Location: chr11:105924583 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.24

Full GRIA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRIA4 p.Ala74Val Uncertain significance ★★ same type
GRIA4 p.Arg35Gln Uncertain significance ★★ ⚠ same type
GRIA4 p.Arg368Cys Uncertain significance ★★ ⚠ same type
GRIA4 p.Arg737Gln Uncertain significance ★★ ⚠ same type
GRIA4 p.Arg872His Uncertain significance ★★ same type
GRIA4 p.Gln205Arg Uncertain significance ★★ ⚠ same type
GRIA4 p.Glu150Lys Uncertain significance ★★ ⚠ same type
GRIA4 p.Gly126Trp Uncertain significance ★★ ⚠ 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/gria4-p-ala554val (accessed [today's date]).

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