CTSF p.Arg421=
c.1263G>T · rs768353764 · VCV590175
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000255%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.051 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor gain · deltas |
| Pangolin | Δ0.24 | gain · loss 0.24 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.16 | GERP -3.5, phastCons 0.93 |
| Overall | ||
| CADD | 11.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,175,158 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000187%
3/1,603,022 alleles · very rare
exomes 2/1,450,864 · genomes 1/152,158 · joint denominator
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.Arg421=
- Coding
- c.1263G>T
- MANE Select
- NM_003793
- dbSNP
- rs768353764
- Type
- single nucleotide variant
- Location
- chr11:66564616 (GRCh38)
- Gene constraint
- LOEUF 1.296 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.78 · 1 PDB
- Residue 421
- an α-helix
Similar variants
- CTSF p.Arg421Gln Uncertain significance ★★ ⚠ same residue
- CTSF p.Arg421Trp Benign/Likely benign ★★ same residue
- CTSF c.1045+1G>T Likely pathogenic ★★ same condition
- CTSF p.Arg217Ter Pathogenic ★★ same condition
- CTSF p.Arg121Pro Uncertain significance ★★ ⚠ same condition
- CTSF p.Arg196Trp Uncertain significance ★★ same condition
- CTSF p.Arg418Cys Uncertain significance ★★ ⚠ same condition
- CTSF p.Arg54Gly 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/ctsf-p-arg421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown