CLN8 p.Ala30=
c.90T>C · rs376382403 · VCV1127614
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
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 -12 | GERP -4 |
| Overall | ||
| CADD | 0.356 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,898 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00031%
5/1,613,984 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,724 |
| European (non-Finnish) | 8.47e-05% | 1,180,045 |
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.Ala30=
- Coding
- c.90T>C
- MANE Select
- NM_018941
- dbSNP
- rs376382403
- Type
- single nucleotide variant
- Location
- chr8:1771144 (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 30
- a UniProt-annotated variant site (in cln8)
Similar variants
- CLN8 p.Ala30Thr Uncertain significance ★★ ⚠ same residue
- CLN8 p.Ala30Ser Uncertain significance ★ ⚠ same residue
- CLN8 p.Ala30Pro 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
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-ala30 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown