CYC1 p.Ile266=
c.798A>C · rs765213313 · VCV2184102
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 1.7 | GERP -3.1, phastCons 1 |
| Overall | ||
| CADD | 6.846 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000617%
9/1,457,992 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,182 |
| Finnishnot grpmax-eligible | 0.00157% | 63,768 |
| European (non-Finnish) | 0.000424% | 235,617 |
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
- CYC1
- Protein
- p.Ile266=
- Coding
- c.798A>C
- MANE Select
- NM_001916
- dbSNP
- rs765213313
- Type
- single nucleotide variant
- Location
- chr8:144097059 (GRCh38)
- Gene constraint
- LOEUF 0.583 · pLI 0.85 (gnomAD)
- Structure
- AlphaFold pLDDT 86.37 · 5 PDB
- Residue 266
- an α-helix
Similar variants
- CYC1 p.Ile266Leu Uncertain significance ★ ⚠ same residue
- CYC1 p.Ala4Val Uncertain significance ★★ ⚠ same type
- CYC1 p.Ala5Thr Uncertain significance ★★ ⚠ same type
- CYC1 p.Arg285Gln Uncertain significance ★★ ⚠ same type
- CYC1 p.Arg287His Uncertain significance ★★ ⚠ same type
- CYC1 p.Arg308Gln Uncertain significance ★★ ⚠ same type
- CYC1 p.Asn159Ser Uncertain significance ★★ ⚠ same type
- CYC1 p.Asp173Asn 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/cyc1-p-ile266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown