EYS p.Thr657=
c.1971T>A · rs1189097279 · VCV751291
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0179%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.86 | GERP -3.1 |
| Overall | ||
| CADD | 0.393 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0179%
South Asian · 15/84,024 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00886%
Overall
0.000967%
15/1,550,838 alleles · ultra-rare
exomes 15/1,398,816 · genomes 0/152,022 · joint denominator
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.Thr657=
- Coding
- c.1971T>A
- MANE Select
- NM_001142800
- dbSNP
- rs1189097279
- Type
- single nucleotide variant
- Location
- chr6:65295915 (GRCh38)
- Gene constraint
- LOEUF 0.96 · pLI <0.01 (gnomAD)
- Residue 657
- the egf-like 7 domain
Similar variants
- 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
- EYS c.1299+2T>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-thr657 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown