CYCS p.Ala51=
c.153C>T · VCV3610550
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00203%, nfe)
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 2.3 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 9.314 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00203%
European (non-Finnish) · 24/1,180,020 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00167%
27/1,613,858 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00203% | 49,168 |
| Finnishnot grpmax-eligible | 0.00156% | 63,978 |
| African / African-American | 0.00134% | 74,826 |
| South Asian | 0.0011% | 91,076 |
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.Ala51=
- Coding
- c.153C>T
- MANE Select
- NM_018947
- Type
- single nucleotide variant
- Location
- chr7:25123967 (GRCh38)
- Gene constraint
- LOEUF 0.335 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 97.95 · 13 PDB
- Residue 51
- an α-helix
Similar variants
- CYCS p.Ala51Gly Uncertain significance ★ ⚠ same residue
- 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.Ile59= Likely benign ★★ same type
- CYCS p.Pro72= Likely benign ★★ same type
- CYCS p.Ala97Asp 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-ala51 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown