CFI p.Val114Ala
c.341T>C · VCV4280550
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3704 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense no call
Conditions
1
CFI-related disorder
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3704 | ambiguous |
|---|---|---|
| REVEL | 0.202 | benign-leaning |
| SaProt | LLR -11.17 | damaging |
| ⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic |
| Overall | ||
| CADD | 24.7 | 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.Val114Ala
- Coding
- c.341T>C
- MANE Select
- NM_000204
- Type
- single nucleotide variant
- Location
- chr4:109764678 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50 · 2 PDB
- Residue 114
- a disulfide bond; the srcr domain; a β-strand
Similar variants
- 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
- CFI p.Asp224Asn 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-val114ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown