EYA4 p.Ser37=
c.111T>C · rs35863035 · VCV44770
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.81%, afr)
Conditions
2
autosomal dominant nonsyndromic hearing loss 10
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 3.4 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 10.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.81%
African / African-American · 1,355/75,034 alleles
Filtering AF
1.73%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.69%
Overall
0.103%
1,659/1,613,966 alleles · low-frequency
exomes 797/1,461,674 · genomes 862/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.81% | 55 |
| Admixed American | 0.215% | 465 |
| Remaining individualsnot grpmax-eligible | 0.147% | 679 |
| Middle Eastern | 0.0825% | 1,212 |
| European (non-Finnish) | 0.00644% | 15,525 |
| South Asian | 0.0022% | 45,538 |
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
- EYA4
- Protein
- p.Ser37=
- Coding
- c.111T>C
- MANE Select
- NM_004100
- dbSNP
- rs35863035
- Type
- single nucleotide variant
- Location
- chr6:133446657 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
- Residue 37
- the 'disordered' region
Similar variants
- EYA4 p.Ser37Asn Uncertain significance ★★ ⚠ same residue
- EYA4 p.Ser37Gly Uncertain significance ★ ⚠ same residue
- EYA4 c.1341-2A>G Likely pathogenic ★★ same condition
- EYA4 c.1739-1G>A Likely pathogenic ★★ same condition
- EYA4 p.Asp194Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
- EYA4 p.Trp81Ter Pathogenic/Likely pathogenic ★★ same condition
- EYA4 c.1282-13A>G Uncertain significance ★★ same condition
- EYA4 c.1340+3A>G Uncertain significance ★★ 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/eya4-p-ser37 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown