CTSD p.Phe229del
c.683TCT[1] · rs1057519591 · VCV375630
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
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 12 | GERP 1.7, phastCons 1 |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,022 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000547%
8/1,461,434 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,022 |
| European (non-Finnish) | 0.000593% | 168,554 |
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.Phe229del
- Coding
- c.683TCT[1]
- MANE Select
- NM_001909
- dbSNP
- rs1057519591
- Type
- Microsatellite
- Location
- chr11:1757340 (GRCh38)
- Gene constraint
- LOEUF 0.886 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.69 · 9 PDB
- Residue 229
- a UniProt-annotated variant site (in cln10); a β-strand; the peptidase a1 domain
Similar variants
- CTSD p.Phe229Ile Pathogenic same residue
- CTSD p.Asn402del Uncertain significance ★★ same condition
- CTSD p.Ser157fs Pathogenic ★ same condition
- CTSD c.472-16_472-15del Likely benign ★ same condition
- CTSD c.228+1G>A Likely pathogenic ★★ same condition
- CTSD p.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
- CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same condition
- CTSD p.Leu11fs 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-phe229del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown