CLN8 p.Asn259=
c.777T>C · rs34814682 · VCV136803
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.04%, afr)
Conditions
4
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 -1.7 | GERP -3.5 |
| Overall | ||
| CADD | 0.825 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.04%
African / African-American · 780/75,032 alleles
Filtering AF
0.979%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.955%
Overall
0.0541%
874/1,614,164 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.04% | 96 |
| Remaining individualsnot grpmax-eligible | 0.0704% | 1,421 |
| Admixed American | 0.0566% | 1,765 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.00549% | 18,216 |
| European (non-Finnish) | 0.000763% | 131,115 |
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.Asn259=
- Coding
- c.777T>C
- MANE Select
- NM_018941
- dbSNP
- rs34814682
- Type
- single nucleotide variant
- Location
- chr8:1780483 (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 259
- the tlc domain
Similar variants
- CLN8 p.Asn259Asp Uncertain significance ★★ ⚠ same residue
- CLN8 p.Asn259Ile Uncertain significance ★ ⚠ same residue
- CLN8 p.Asn259Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLN8 p.Asn259Thr 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
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-asn259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown