REST p.Pro141=
c.423C>T · rs1387036063 · VCV2177821
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.054 | GERP -4.5, phastCons 0.002 |
| Overall | ||
| CADD | 4.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.00031%
5/1,613,944 alleles · ultra-rare
exomes 4/1,461,818 · genomes 1/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 0.000254% | 393,342 |
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.Pro141=
- Coding
- c.423C>T
- MANE Select
- NM_005612
- dbSNP
- rs1387036063
- Type
- single nucleotide variant
- Location
- chr4:56911061 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.53 · 3 PDB
- Residue 141
- the 'disordered' region
Similar variants
- REST p.Pro141Arg 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
- REST p.Arg199Gly 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-pro141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown