CLN3 p.Pro239=
c.717T>C · rs2046160732 · VCV1585309
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.17 | GERP 0.24 |
| Overall | ||
| CADD | 8.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,856 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.000558%
9/1,612,508 alleles · ultra-rare
exomes 9/1,460,274 · genomes 0/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,607 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,438 |
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
- CLN3
- Protein
- p.Pro239=
- Coding
- c.717T>C
- MANE Select
- NM_001042432
- dbSNP
- rs2046160732
- Type
- single nucleotide variant
- Location
- chr16:28484079 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 81.81
- Residue 239
- the 'disordered' region
Similar variants
- CLN3 c.1056+1G>A Likely pathogenic ★★ same condition
- CLN3 c.1056+1G>T Likely pathogenic ★★ same condition
- CLN3 c.1056+3A>C Pathogenic/Likely pathogenic ★★ same condition
- CLN3 c.1197+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CLN3 c.1198-1G>T Pathogenic/Likely pathogenic ★★ same condition
- CLN3 c.125+1G>C Pathogenic ★★ same condition
- CLN3 c.222+1G>A Likely pathogenic ★★ same condition
- CLN3 c.46+1G>A 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/cln3-p-pro239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown