CSTB p.Gly4=
c.12G>A · rs1555888494 · VCV462912
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.77e-05%, nfe)
Conditions
1
progressive myoclonus epilepsy
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 -6.8 | GERP -4.1 |
| Overall | ||
| CADD | 0.965 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.77e-05%
European (non-Finnish) · 1/1,140,348 alleles
Overall
7.27e-05%
1/1,376,460 alleles · very rare
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
- CSTB
- Protein
- p.Gly4=
- Coding
- c.12G>A
- MANE Select
- NM_000100
- dbSNP
- rs1555888494
- Type
- single nucleotide variant
- Location
- chr21:43776258 (GRCh38)
- Gene constraint
- LOEUF 1.681 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 95.81 · 3 PDB
- Residue 4
- a functional site (reactive site); a UniProt-annotated variant site (in epm1)
Similar variants
- CSTB p.Gly4Arg Likely pathogenic ★ same residue
- CSTB p.Gly4Trp Likely pathogenic ★ same residue
- CSTB c.67-1G>C Pathogenic ★★ same condition
- CSTB p.Arg68Ter Pathogenic ★★ same condition
- CSTB p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
- CSTB p.Gln46Ter Pathogenic/Likely pathogenic ★★ same condition
- CSTB p.Ala49Thr Uncertain significance ★★ same condition
- CSTB p.Ala90Thr 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/cstb-p-gly4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown