CLN6 p.Arg35Pro
c.104G>C · VCV4822882
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.211 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -0.8 |
| Overall | ||
| CADD | 0.924 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,364 alleles
Overall
0.000142%
1/701,994 alleles · ultra-rare
exomes 0/549,628 · genomes 1/152,366 · joint denominator
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
- CLN6
- Protein
- p.Arg35Pro
- Coding
- c.104G>C
- MANE Select
- NM_017882 · reported on NM_001411068
- Type
- single nucleotide variant
- Location
- chr15:68256765 (GRCh38)
- Gene constraint
- LOEUF 1.015 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.86
Similar variants
- CLN6 p.Asp35Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLN6 p.Asp35= Likely benign ★ same residue
- CLN6 c.297+1G>A Pathogenic/Likely pathogenic ★★ same type
- CLN6 c.486+1G>A Likely pathogenic ★★ same type
- CLN6 c.543-1G>A Likely pathogenic ★★ same type
- CLN6 c.665+1G>A Pathogenic/Likely pathogenic ★★ same type
- CLN6 c.665+1G>T Likely pathogenic ★★ same type
- CLN6 c.83+1G>C Likely pathogenic ★★ same type
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/cln6-p-arg35pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown