EYA4 p.Ser288Ter
c.863C>G · rs2128674545 · VCV2440127
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 20 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EYA4
- Protein
- p.Ser288Ter
- Coding
- c.863C>G
- MANE Select
- NM_004100
- dbSNP
- rs2128674545
- Type
- single nucleotide variant
- Location
- chr6:133468624 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.79
- Residue 288
- a UniProt-annotated variant site (in dfna10)
Similar variants
- EYA4 c.1341-2A>G Likely pathogenic ★★ same type
- EYA4 c.1739-1G>A Likely pathogenic ★★ same type
- EYA4 p.Asp194Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
- EYA4 p.Gln513Ter Pathogenic/Likely pathogenic ★★ same type
- EYA4 p.Trp81Ter Pathogenic/Likely pathogenic ★★ same type
- EYA4 c.1282-13A>G Uncertain significance ★★ same type
- EYA4 c.1340+3A>G Uncertain significance ★★ same type
- EYA4 c.1739-118G>A Uncertain significance ★★ 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/eya4-p-ser288ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown