CTSF p.Trp457Ter
c.1370G>A · rs888414145 · VCV1331400
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 10 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.26 | loss · gain 0.05 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 44.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,920 |
| European (non-Finnish) | 8.48e-05% | 1,179,846 |
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
- CTSF
- Protein
- p.Trp457Ter
- Coding
- c.1370G>A
- MANE Select
- NM_003793
- dbSNP
- rs888414145
- Type
- single nucleotide variant
- Location
- chr11:66564098 (GRCh38)
- Gene constraint
- LOEUF 1.296 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.78 · 1 PDB
- Residue 457
- a disulfide bond
Similar variants
- CTSF c.1045+1G>T Likely pathogenic ★★ same type
- CTSF p.Arg217Ter Pathogenic ★★ same type
- CTSF p.Ala22Ser Uncertain significance ★★ ⚠ same type
- CTSF p.Arg121Pro Uncertain significance ★★ ⚠ same type
- CTSF p.Arg196Gln Uncertain significance ★★ ⚠ same type
- CTSF p.Arg196Trp Uncertain significance ★★ ⚠ same type
- CTSF p.Arg205Trp Uncertain significance ★★ ⚠ same type
- CTSF p.Arg413Cys Uncertain significance ★★ ⚠ same type
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/ctsf-p-trp457ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown