CLN8 p.Leu188=
c.562C>T · rs587780318 · VCV128789
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
neuronal ceroid lipofuscinosis
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 1 | GERP 1.8, phastCons 0.023 |
| Overall | ||
| CADD | 3.827 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,904 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.000929%
15/1,614,156 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,904 |
| African / African-American | 0.00133% | 74,950 |
| European (non-Finnish) | 0.0011% | 90,774 |
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.Leu188=
- Coding
- c.562C>T
- MANE Select
- NM_018941
- dbSNP
- rs587780318
- Type
- single nucleotide variant
- Location
- chr8:1780268 (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 188
- the tlc domain
Similar variants
- CLN8 p.Leu188fs Pathogenic/Likely pathogenic ★★ 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
- CLN8 p.Gln99Ter Pathogenic/Likely 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-leu188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown