CFI p.Ser449=
c.1347C>T · rs141961923 · VCV1127140
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00822%, nfe)
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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.5 |
| Overall | ||
| CADD | 1.725 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00822%
European (non-Finnish) · 97/1,180,024 alleles
Filtering AF
0.00689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.00632%
102/1,614,046 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00822% | 12,165 |
| African / African-American | 0.004% | 24,975 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| Finnishnot grpmax-eligible | 0.00156% | 64,038 |
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.Ser449=
- Coding
- c.1347C>T
- MANE Select
- NM_000204
- dbSNP
- rs141961923
- Type
- single nucleotide variant
- Location
- chr4:109746304 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50 · 2 PDB
- Residue 449
- 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-ser449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown