CTSD c.68+5A>C
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00254%, eas)
Conditions
1
neuronal ceroid lipofuscinosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +5 | donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -0.56, phastCons 0.99 |
| Non-coding constraint | Z 3.89 | 1 kb window · o/e 0.76 · regional · uncalibrated |
| Overall | ||
| CADD | 14.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00254%
East Asian · 1/39,386 alleles
Filtering AF
0.000255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000164%
Overall
0.000583%
8/1,372,456 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00254% | 39,386 |
| European (non-Finnish) | 0.000613% | 163,217 |
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
- CTSD
- Coding
- c.68+5A>C
- MANE Select
- NM_001909
- dbSNP
- rs1444419430
- Type
- single nucleotide variant
- Location
- chr11:1763787 (GRCh38)
- Gene constraint
- LOEUF 0.886 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.69 · 9 PDB
Similar variants
- CTSD c.228+1G>A Likely pathogenic ★★ same condition
- CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same condition
- CTSD c.828-3C>A Uncertain significance ★★ same condition
- CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same condition
- CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
- CTSD p.Ala18Thr Uncertain significance ★★ ⚠ same condition
- CTSD p.Ala239Val Uncertain significance ★★ ⚠ same condition
- CTSD p.Arg176Lys Uncertain significance ★★ ⚠ 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/ctsd-c-68-plus-5a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown