CTSD p.Val308=
c.924G>A · rs1554962286 · VCV452877
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Conditions
1
neuronal ceroid lipofuscinosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.09 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.14 | phastCons 0.001 |
| Overall | ||
| CADD | 9.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,342 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000206%
3/1,458,508 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
- CTSD
- Protein
- p.Val308=
- Coding
- c.924G>A
- MANE Select
- NM_001909
- dbSNP
- rs1554962286
- Type
- single nucleotide variant
- Location
- chr11:1754042 (GRCh38)
- Gene constraint
- LOEUF 0.886 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.69 · 9 PDB
- Residue 308
- an α-helix; the peptidase a1 domain
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-p-val308 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown