CLN3 p.Pro81=
c.243G>C · rs779165392 · VCV1114008
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
2
neuronal ceroid lipofuscinosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.172 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor loss · deltas |
| Pangolin | Δ0.23 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.16 | GERP -2.3, phastCons 0.001 |
| Overall | ||
| CADD | 1.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,010 alleles
Overall
6.84e-05%
1/1,461,872 alleles · very rare
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.Pro81=
- Coding
- c.243G>C
- MANE Select
- NM_001042432
- dbSNP
- rs779165392
- Type
- single nucleotide variant
- Location
- chr16:28488642 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 81.81
Similar variants
- CLN3 p.Pro81Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLN3 p.Pro81fs Pathogenic/Likely pathogenic ★★ same residue
- 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
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-pro81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown