EPHB4 p.Tyr596Ter
c.1788T>A · rs749503755 · VCV1806103
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
capillary malformation-arteriovenous malformation 2
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 |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 17 |
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.73 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -7.1 | GERP -5 |
| Overall | ||
| CADD | 24.1 | 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
- EPHB4
- Protein
- p.Tyr596Ter
- Coding
- c.1788T>A
- MANE Select
- NM_004444
- dbSNP
- rs749503755
- Type
- single nucleotide variant
- Location
- chr7:100813177 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 596
- a UniProt-annotated variant site (in cmavm2)
Similar variants
- EPHB4 c.2484+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Arg365Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Arg739Ter Pathogenic ★★ same condition
- EPHB4 p.Arg763Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Gln580Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Glu664Lys Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Trp72Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Cys285Arg 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/ephb4-p-tyr596ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown