EYS p.Cys554Arg
c.1660T>C · VCV4892695
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3507 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3507 | ambiguous |
|---|---|---|
| REVEL | 0.185 | benign-leaning |
| SaProt | — | not scored · why |
| Splicing | ||
| SpliceAI | Δ0.28 | acceptor loss, 11 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 0.52 | GERP -0.26 |
| Regional constraint | o/e 1.08 | unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic |
| Overall | ||
| CADD | 12.86 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
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
- EYS
- Protein
- p.Cys554Arg
- Coding
- c.1660T>C
- MANE Select
- NM_001142800
- Type
- single nucleotide variant
- Location
- chr6:65335086 (GRCh38)
- Gene constraint
- LOEUF 0.96 · pLI <0.01 (gnomAD)
Similar variants
- EYS p.Cys554Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same type
- EYS c.1056+3A>C Likely pathogenic ★★ same type
- EYS c.1057-1G>A Likely pathogenic ★★ same type
- EYS c.1184+1G>A Pathogenic/Likely pathogenic ★★ same type
- EYS c.1184+1G>T Likely pathogenic ★★ same type
- EYS c.1185-1G>A Likely pathogenic ★★ same type
- EYS c.1299+1G>T 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/eys-p-cys554arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown