EYA1 p.Arg461=
c.1383G>A · rs540131742 · VCV1621540
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
Conditions
1
branchio-oto-renal syndrome
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 1.7 | GERP -2.9, phastCons 1 |
| Overall | ||
| CADD | 9.095 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,060 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.00322%
52/1,613,960 alleles · ultra-rare
exomes 43/1,461,670 · genomes 9/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| Admixed American | 0.01% | 10,003 |
| South Asian | 0.00988% | 10,120 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| African / African-American | 0.00267% | 37,513 |
| European (non-Finnish) | 0.00212% | 47,196 |
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
- EYA1
- Protein
- p.Arg461=
- Coding
- c.1383G>A
- MANE Select
- NM_000503
- dbSNP
- rs540131742
- Type
- single nucleotide variant
- Location
- chr8:71215706 (GRCh38)
- Gene constraint
- LOEUF 0.291 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.68
Similar variants
- EYA1 c.1050+1G>T Pathogenic ★★ same condition
- EYA1 c.1051-2A>G Pathogenic ★★ same condition
- EYA1 c.1199+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EYA1 c.1200-1G>A Pathogenic ★★ same condition
- EYA1 c.1360+5G>A Pathogenic/Likely pathogenic ★★ same condition
- EYA1 c.1361-1G>A Pathogenic ★★ same condition
- EYA1 c.1597+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EYA1 c.1698+1G>T Pathogenic ★★ same condition
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/eya1-p-arg461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown