EYA4 p.Pro399=
c.1197C>A · rs373910569 · VCV1618028
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00402%, afr)
Conditions
2
Cardiovascular phenotype
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 -1.1 | GERP -4.2, phastCons 0.001 |
| Overall | ||
| CADD | 11.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00402%
African / African-American · 3/74,564 alleles
Filtering AF
0.00107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000496%
Overall
0.000188%
3/1,596,588 alleles · very rare
exomes 0/1,444,492 · genomes 3/152,096 · 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
- EYA4
- Protein
- p.Pro399=
- Coding
- c.1197C>A
- MANE Select
- NM_004100
- dbSNP
- rs373910569
- Type
- single nucleotide variant
- Location
- chr6:133506111 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
- Residue 399
- a UniProt-annotated variant site (in dfna10)
Similar variants
- EYA4 p.Pro399Leu 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
- EYA4 c.970+5A>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-pro399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown