EPHB4 c.964+3A>T
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
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/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.75 | donor loss · deltas |
| Pangolin | Δ0.72 | loss · gain 0.45 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -5, phastCons 1 |
| Non-coding constraint | Z -0.95 | 1 kb window · o/e 1.07 · regional · uncalibrated |
| Overall | ||
| CADD | 23.0 | PHRED · no single calibrated threshold — expert panels disagree |
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
- Coding
- c.964+3A>T
- MANE Select
- NM_004444
- dbSNP
- rs2485037560
- Type
- single nucleotide variant
- Location
- chr7:100820138 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
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-c-964-plus-3a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown