CFD p.Glu219=
c.657G>A · rs577832450 · VCV1640796
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, eas)
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 0.32 | GERP -3.8, phastCons 0.95 |
| Overall | ||
| CADD | 4.938 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
East Asian · 6/40,764 alleles
Filtering AF
0.00637%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00436%
Overall
0.000717%
11/1,533,120 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0147% | 6,794 |
| Remaining individualsnot grpmax-eligible | 0.00335% | 29,889 |
| European (non-Finnish) | 0.000262% | 381,369 |
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
- CFD
- Protein
- p.Glu219=
- Coding
- c.657G>A
- MANE Select
- NM_001928
- dbSNP
- rs577832450
- Type
- single nucleotide variant
- Location
- chr19:863133 (GRCh38)
- Gene constraint
- LOEUF 1.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.19 · 40 PDB
- Residue 219
- a disulfide bond; the peptidase s1 domain; a β-strand
Similar variants
- CFD p.Glu219Lys Uncertain significance ★ ⚠ same residue
- CFD p.Glu219_Val222del Uncertain significance ★ same residue
- CFD c.212+2T>G Likely pathogenic ★★ same type
- CFD c.56-1G>C Likely pathogenic ★★ same type
- CFD p.Tyr95Ter Pathogenic ★★ same type
- ELANE p.Gly203Arg Pathogenic ★★ same type
- ELANE p.Ser126Leu Pathogenic ★★ ⚠ same type
- CFD p.Ala100Pro 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/cfd-p-glu219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown