CFI p.Arg336=
c.1006C>A · VCV3677477
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.38 | donor loss, 38 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.39 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP -0.33, phastCons 1 |
| Overall | ||
| CADD | 2.337 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,998 alleles
Overall
0.000205%
3/1,461,354 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,998 |
| South Asian | 0.0011% | 91,064 |
| European (non-Finnish) | 8.48e-05% | 1,179,558 |
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.Arg336=
- Coding
- c.1006C>A
- MANE Select
- NM_000204
- Type
- single nucleotide variant
- Location
- chr4:109749537 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50 · 2 PDB
- Residue 336
- a disulfide bond
Similar variants
- CFI p.Arg336Gly Uncertain significance ★★ ⚠ same residue
- CFI p.Arg336Gln 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
- CFI p.Arg187Ter 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-arg336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown