CTSD p.Phe231del
c.692_694del · rs1478615059 · VCV1518691
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
neuronal ceroid lipofuscinosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 20.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,920 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.00031%
5/1,613,308 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,460 |
| Admixed American | 0.00167% | 59,982 |
| European (non-Finnish) | 0.00017% | 589,842 |
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.Phe231del
- Coding
- c.692_694del
- MANE Select
- NM_001909
- dbSNP
- rs1478615059
- Type
- Deletion
- Location
- chr11:1757334 (GRCh38)
- Gene constraint
- LOEUF 0.886 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.69 · 9 PDB
- Residue 231
- a β-strand; the peptidase a1 domain
Similar variants
- CTSD p.Phe231= Likely benign ★ same residue
- CTSD p.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
- CTSD p.Val318fs Pathogenic/Likely pathogenic ★★ same condition
- CTSD p.Val52fs Pathogenic/Likely pathogenic ★★ same condition
- CTSD p.Pro381fs Uncertain significance ★★ same condition
- CTSD c.828-14_828-13del Benign/Likely benign ★★ same condition
- CTSD c.824_827+30del Likely pathogenic ★ same condition
- CTSD p.Ala18fs 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/ctsd-p-phe231del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown