REST p.Ala620=
c.1860G>A · rs376567179 · VCV1597294
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00178%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.5 | GERP -4 |
| Overall | ||
| CADD | 0.571 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
Admixed American · 1/56,172 alleles
Filtering AF
0.000544%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00043%
Overall
0.000874%
14/1,601,282 alleles · very rare
exomes 12/1,450,202 · genomes 2/151,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00178% | 56,172 |
| South Asian | 0.00113% | 88,798 |
| European (non-Finnish) | 0.00102% | 98,069 |
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.Ala620=
- Coding
- c.1860G>A
- MANE Select
- NM_005612
- dbSNP
- rs376567179
- Type
- single nucleotide variant
- Location
- chr4:56930718 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.53 · 3 PDB
- Residue 620
- the 'disordered' region; a UniProt-annotated variant site (in gingf5)
Similar variants
- REST p.Ala620Val 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-ala620 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown