CFD p.Ala246=
c.738C>G · rs772161967 · VCV1535779
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00543%, afr)
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 | GERP -4.9 |
| Overall | ||
| CADD | 6.293 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00543%
African / African-American · 4/73,712 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.000389%
6/1,543,974 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00543% | 18,428 |
| Admixed American | 0.00195% | 51,296 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,332 |
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.Ala246=
- Coding
- c.738C>G
- MANE Select
- NM_001928
- dbSNP
- rs772161967
- Type
- single nucleotide variant
- Location
- chr19:863214 (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 246
- the peptidase s1 domain; an α-helix
Similar variants
- CFD p.Ala246Val 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
- CFD p.Ala129Thr 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-ala246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown