CLN8 p.Gln100=
c.300G>A · rs148988002 · VCV700161
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 3.5 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 8.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| European (non-Finnish)grpmax | 0.00576% | 17,354 |
| Finnishnot grpmax-eligible | 0.00469% | 21,344 |
| South Asian | 0.0011% | 91,076 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- CLN8
- Protein
- p.Gln100=
- Coding
- c.300G>A
- MANE Select
- NM_018941
- dbSNP
- rs148988002
- Type
- single nucleotide variant
- Location
- chr8:1771354 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.47 · 3 PDB
- Residue 100
- the tlc domain
Disease context
neuronal ceroid lipofuscinosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: neuronal ceroid lipofuscinosis 8 northern epilepsy variantneuronal ceroid lipofuscinosis
For CLN8 disease (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy
Similar variants
- CLN8 p.Gln100Ter Pathogenic ★ same residue
- CLN8 p.Gln100Arg Uncertain significance ★ ⚠ same residue
- CLN8 p.Arg204Cys Pathogenic/Likely pathogenic ★★ same condition
- CLN8 p.Arg204His Likely pathogenic ★★ same condition
- CLN8 p.Arg24Gly Pathogenic ★★ same condition
- CLN8 p.Arg70Cys Pathogenic/Likely pathogenic ★★ same condition
- CLN8 p.Arg70His Pathogenic/Likely pathogenic ★★ same condition
- CLN8 p.Gln255Ter Pathogenic ★★ 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/cln8-p-gln100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown