CYCS p.Ile59=
c.177C>T · rs542396973 · VCV2064953
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, 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 4.8 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 8.619 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00715%
Overall
0.00372%
60/1,614,004 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| East Asian | 0.00668% | 14,967 |
| South Asian | 0.00439% | 22,773 |
| European (non-Finnish) | 0.00415% | 24,082 |
| Admixed American | 0.00167% | 60,012 |
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
- CYCS
- Protein
- p.Ile59=
- Coding
- c.177C>T
- MANE Select
- NM_018947
- dbSNP
- rs542396973
- Type
- single nucleotide variant
- Location
- chr7:25123842 (GRCh38)
- Gene constraint
- LOEUF 0.335 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 97.95 · 13 PDB
Similar variants
- CYCS p.Gly42Ser Likely pathogenic ★★ same type
- CYCS p.Ala52Thr Uncertain significance ★★ ⚠ same type
- CYCS p.Leu33Val Uncertain significance ★★ ⚠ same type
- CYCS c.-6T>G Benign/Likely benign ★★ same type
- CYCS p.Ala51= Likely benign ★★ same type
- CYCS p.Pro72= Likely benign ★★ same type
- CYCS p.Ala97Asp Likely pathogenic ★ ⚠ same type
- CYCS p.Leu65Val 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/cycs-p-ile59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown