EYS p.Glu645=
c.1935A>G · rs761881037 · VCV1147447
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00235%, 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 0.19 | GERP 0.29 |
| Overall | ||
| CADD | 1.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00235%
European (non-Finnish) · 27/1,146,518 alleles
Filtering AF
0.00161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00138%
Overall
0.00187%
29/1,551,068 alleles · very rare
exomes 28/1,399,058 · genomes 1/152,010 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00235% | 42,464 |
| African / African-American | 0.00137% | 73,002 |
| South Asian | 0.00119% | 84,056 |
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
- EYS
- Protein
- p.Glu645=
- Coding
- c.1935A>G
- MANE Select
- NM_001142800
- dbSNP
- rs761881037
- Type
- single nucleotide variant
- Location
- chr6:65295951 (GRCh38)
- Gene constraint
- LOEUF 0.96 · pLI <0.01 (gnomAD)
- Residue 645
- the egf-like 7 domain
Similar variants
- EYS p.Glu645Ter Likely pathogenic ★ same residue
- EYS p.Glu645Lys Uncertain significance ★ ⚠ 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
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-glu645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown