REST p.Val422Ile
c.1264G>A · VCV4152766
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.342 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.342 | ambiguous |
|---|---|---|
| REVEL | 0.172 | moderately benign-leaning |
| SaProt | LLR -5.95 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 1.11 | unconstrained · MANE · 1,930 bp · p 0.0028 · regional, not allelic |
| Overall | ||
| CADD | 25.9 | 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
- REST
- Protein
- p.Val422Ile
- Coding
- c.1264G>A
- MANE Select
- NM_005612
- Type
- single nucleotide variant
- Location
- chr4:56930122 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.53 · 3 PDB
Similar variants
- REST p.Val422= Likely benign ★★ same residue
- REST p.Ala198Val Uncertain significance ★★ ⚠ same condition
- REST p.Ala25Ser Uncertain significance ★★ ⚠ same condition
- REST p.Ala642Val Uncertain significance ★★ ⚠ same condition
- REST p.Arg199Gly Uncertain significance ★★ ⚠ same condition
- REST p.Arg217Cys Uncertain significance ★★ ⚠ same condition
- REST p.Asn282Ser Uncertain significance ★★ ⚠ same condition
- REST p.Asn390Ser Uncertain significance ★★ ⚠ 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/rest-p-val422ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown