Is EPHB4 p.Arg240fs (c.719del) pathogenic?

EPHB4 p.Arg240fs (c.719del) is classified Likely pathogenic in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-29). Associated with EPHB4-related disorder.

What condition is associated with EPHB4 p.Arg240fs (c.719del)?

EPHB4 p.Arg240fs (c.719del) is associated with EPHB4-related disorder (ClinVar).

EPHB4 p.Arg240fs

c.719del · VCV4897178

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

EPHB4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.7	GERP -4.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EPHB4
Protein: p.Arg240fs
Coding: c.719del
MANE Select: NM_004444
Type: Deletion
Location: chr7:100822360 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 240: a UniProt-annotated variant site (in cmavm2)

Full EPHB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EPHB4-related disorder

Similar variants

EPHB4 p.Ala476fs Likely pathogenic ★ same condition
EPHB4 p.Cys239fs Likely pathogenic ★ same condition
EPHB4 p.Glu655fs Pathogenic ★ same condition
EPHB4 p.Gly221fs Likely pathogenic ★ same condition
EPHB4 p.Pro151fs Likely pathogenic ★ same condition
EPHB4 p.Arg240His Uncertain significance ★ ⚠ same residue
EPHB4 p.Arg240Pro Uncertain significance ★ ⚠ same residue
EPHB4 p.Gln858fs 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-arg240fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown