CLN5 p.Phe139=
c.417C>T · rs371229525 · VCV377691
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0254%, afr)
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 0.65 | GERP -0.096, phastCons 1 |
| Overall | ||
| CADD | 12.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0254%
African / African-American · 19/74,924 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00118%
19/1,614,072 alleles · ultra-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
- CLN5
- Protein
- p.Phe139=
- Coding
- c.417C>T
- MANE Select
- NM_006493
- dbSNP
- rs371229525
- Type
- single nucleotide variant
- Location
- chr13:76995979 (GRCh38)
- Gene constraint
- LOEUF 1.197 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 1 PDB
- Residue 139
- a disulfide bond
Similar variants
- CLN5 p.Phe139Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLN5 p.Phe139Ser Uncertain significance ★ ⚠ same residue
- 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
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-phe139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown