EPHB4 p.Arg394Ter
c.1180C>T · rs994651018 · VCV618629
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
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 |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 17 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 36.0 | 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
- EPHB4
- Protein
- p.Arg394Ter
- Coding
- c.1180C>T
- MANE Select
- NM_004444
- dbSNP
- rs994651018
- Type
- single nucleotide variant
- Location
- chr7:100819674 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 394
- a UniProt-annotated variant site (in cmavm2); the fibronectin type-iii 1 domain
Similar variants
- EPHB4 p.Arg394Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- EPHB4 c.1691+1G>A Pathogenic/Likely pathogenic ★★ same type
- EPHB4 c.2484+1G>A Pathogenic/Likely pathogenic ★★ same type
- EPHB4 p.Arg269Ter Pathogenic/Likely pathogenic ★★ same type
- EPHB4 p.Arg365Ter Pathogenic/Likely pathogenic ★★ same type
- EPHB4 p.Arg431Ter Pathogenic ★★ same type
- EPHB4 p.Arg739Gln Pathogenic ★★ same type
- EPHB4 p.Arg739Ter Pathogenic ★★ 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/ephb4-p-arg394ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown