REST p.Ala147=
c.441G>A · rs546925491 · VCV1140445
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.52 | GERP -4.5 |
| Overall | ||
| CADD | 3.417 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,888 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.00031%
5/1,614,176 alleles · very rare
exomes 4/1,461,880 · genomes 1/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,444 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| European (non-Finnish) | 8.47e-05% | 1,180,040 |
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
- REST
- Protein
- p.Ala147=
- Coding
- c.441G>A
- MANE Select
- NM_005612
- dbSNP
- rs546925491
- Type
- single nucleotide variant
- Location
- chr4:56911079 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.53 · 3 PDB
- Residue 147
- the 'disordered' region; the 'interaction with zfp90' region
Similar variants
- REST p.Ala147Thr Uncertain significance ★ ⚠ same residue
- REST p.Ala147Val Uncertain significance ★ ⚠ same residue
- REST p.Ala198Val Uncertain significance ★★ ⚠ same type
- REST p.Ala25Ser Uncertain significance ★★ ⚠ same type
- REST p.Ala637Ser Uncertain significance ★★ ⚠ same type
- REST p.Ala642Val Uncertain significance ★★ ⚠ same type
- REST p.Ala678Ser Uncertain significance ★★ ⚠ same type
- REST p.Ala998Thr 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/rest-p-ala147 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown