CFI p.Val230Glu
c.689T>A · VCV4280554
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2306 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
CFI-related disorder
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2306 | likely benign ⚠ discordant with ClinVar |
|---|---|---|
| REVEL | 0.897 | moderately pathogenic-leaning |
| SaProt | LLR -5.93 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic |
| Overall | ||
| CADD | 24.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CFI
- Protein
- p.Val230Glu
- Coding
- c.689T>A
- MANE Select
- NM_000204
- Type
- single nucleotide variant
- Location
- chr4:109760606 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50 · 2 PDB
- Residue 230
- a disulfide bond; the ldl-receptor class a 1 domain
Similar variants
- CFI p.Val230Met Uncertain significance ★★ ⚠ same residue
- CFI p.Arg187Ter Pathogenic/Likely pathogenic ★★ same condition
- CFI p.Arg474Ter Pathogenic/Likely pathogenic ★★ same condition
- CFI p.Trp145Ter Pathogenic ★★ same condition
- CFI p.Ala153Thr Uncertain significance ★★ ⚠ same condition
- CFI p.Ala76Gly Uncertain significance ★★ ⚠ same condition
- CFI p.Arg317Gln Uncertain significance ★★ ⚠ same condition
- CFI p.Arg502Cys Uncertain significance ★★ ⚠ same condition
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-val230glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown