CYBA p.Glu53Asp
c.159G>C · VCV3366326
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9889 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9889 | likely pathogenic · top 7% in CYBA |
|---|---|---|
| REVEL | 0.705 | pathogenic-leaning |
| SaProt | LLR -7.46 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.68 | GERP -2.8, phastCons 1 |
| Regional constraint | o/e 1.20 | unconstrained · MANE · 7,657 bp · p 0.00077 · regional, not allelic |
| Overall | ||
| CADD | 22.7 | 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
- CYBA
- Protein
- p.Glu53Asp
- Coding
- c.159G>C
- MANE Select
- NM_000101
- Type
- single nucleotide variant
- Location
- chr16:88647145 (GRCh38)
- Gene constraint
- LOEUF 1.726 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.28 · 7 PDB
- Residue 53
- a UniProt-annotated variant site (in cgd4); an α-helix
Similar variants
- CYBA p.Glu53= Likely benign ★ same residue
- CYBA c.128+2T>C Likely pathogenic ★★ same type
- CYBA c.204-2A>G Pathogenic/Likely pathogenic ★★ same type
- CYBA c.287+1G>T Pathogenic/Likely pathogenic ★★ same type
- CYBA c.287+2T>C Pathogenic/Likely pathogenic ★★ same type
- CYBA c.288-1G>T Pathogenic/Likely pathogenic ★★ same type
- CYBA c.369+1G>A Likely pathogenic ★★ same type
- CYBA c.58+2T>C Pathogenic/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/cyba-p-glu53asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown