CLN5 p.Ala8=
c.24A>G · rs757756318 · VCV1145429
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00204%, nfe)
Conditions
2
Inborn genetic diseases
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 -1.4 | GERP -2 |
| Overall | ||
| CADD | 7.324 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00204%
European (non-Finnish) · 24/1,178,940 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00155%
25/1,610,832 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00204% | 49,122 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,268 |
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
- CLN5
- Protein
- p.Ala8=
- Coding
- c.24A>G
- MANE Select
- NM_006493
- dbSNP
- rs757756318
- Type
- single nucleotide variant
- Location
- chr13:76992122 (GRCh38)
- Gene constraint
- LOEUF 1.197 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 1 PDB
Similar variants
- CLN5 c.174-2A>G Likely pathogenic ★★ same condition
- CLN5 p.Arg150Ter Pathogenic ★★ same condition
- CLN5 p.Arg63His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CLN5 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
- CLN5 p.Asn143Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CLN5 p.Cys77Tyr Likely pathogenic ★★ ⚠ same condition
- CLN5 p.Gln183Ter Pathogenic/Likely pathogenic ★★ same condition
- CLN5 p.Gln194Ter 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/cln5-p-ala8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown