CLN5 p.Pro347=
c.1041T>C · rs36038805 · VCV128779
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 9.86%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
3
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 0.025 | GERP -5.1, phastCons 0.96 |
| Overall | ||
| CADD | 6.275 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.86%
African / African-American · 7,347/74,500 alleles
Filtering AF
9.67%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.6%
Overall
0.516%
8,276/1,603,772 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.86% | 10 |
| Admixed American | 0.711% | 141 |
| Remaining individualsnot grpmax-eligible | 0.597% | 168 |
| Middle Eastern | 0.232% | 430 |
| South Asian | 0.0134% | 7,461 |
| European (non-Finnish) | 0.00961% | 10,404 |
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.Pro347=
- Coding
- c.1041T>C
- MANE Select
- NM_006493
- dbSNP
- rs36038805
- Type
- single nucleotide variant
- Location
- chr13:77000933 (GRCh38)
- Gene constraint
- LOEUF 1.197 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 1 PDB
Similar variants
- CLN5 p.Pro347_Leu348= Uncertain significance ★ same residue
- CLN5 p.Pro347fs 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.Cys144Tyr 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-pro347 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown