CFI p.Cys247=
c.741T>C · rs1308535667 · VCV1648211
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.32 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.18 | GERP -3, phastCons 0.004 |
| Overall | ||
| CADD | 6.187 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,024 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000618%
9/1,455,344 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,008 |
| African / African-American | 0.00134% | 74,902 |
| European (non-Finnish) | 0.000426% | 234,839 |
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.Cys247=
- Coding
- c.741T>C
- MANE Select
- NM_000204
- dbSNP
- rs1308535667
- Type
- single nucleotide variant
- Location
- chr4:109760554 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50 · 2 PDB
- Residue 247
- a disulfide bond; the ldl-receptor class a 1 domain; a β-strand
Similar variants
- CFI p.Cys247Gly Pathogenic ★ same residue
- CFI p.Cys247Phe Uncertain significance ★ ⚠ same residue
- CFI p.Cys247Tyr Uncertain significance ★ ⚠ same residue
- 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
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-cys247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown