CFI p.Tyr539=
c.1617T>C · rs769602593 · VCV1623584
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0822%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Pangolin | Δ0.27 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.179 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0822%
Middle Eastern · 5/6,082 alleles
Filtering AF
0.0323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00186%
30/1,614,102 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0822% | 1,216 |
| Admixed American | 0.0283% | 3,530 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| European (non-Finnish) | 0.000508% | 196,671 |
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
- CFI
- Protein
- p.Tyr539=
- Coding
- c.1617T>C
- MANE Select
- NM_000204
- dbSNP
- rs769602593
- Type
- single nucleotide variant
- Location
- chr4:109741028 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50 · 2 PDB
- Residue 539
- a β-strand; a disulfide bond; the peptidase s1 domain
Similar variants
- CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same type
- CFI c.57+1G>C Likely pathogenic ★★ same type
- CFI c.658+1G>A Likely pathogenic ★★ same type
- CFI c.905-1G>C Likely pathogenic ★★ same type
- CFI p.Ala258Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- CFI p.Arg187Ter Pathogenic/Likely pathogenic ★★ same type
- CFI p.Arg474Ter Pathogenic/Likely pathogenic ★★ same type
- CFI p.His380Arg Pathogenic/Likely pathogenic ★★ 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/cfi-p-tyr539 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown