Is EPHB4 p.Cys239fs (c.717_727del) pathogenic?

EPHB4 p.Cys239fs (c.717727del) is classified Likely pathogenic in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). Absent from gnomAD; Associated with EPHB4-related disorder.

What condition is associated with EPHB4 p.Cys239fs (c.717_727del)?

EPHB4 p.Cys239fs (c.717_727del) is associated with EPHB4-related disorder (ClinVar).

How common is EPHB4 p.Cys239fs (c.717_727del) in the general population?

EPHB4 p.Cys239fs (c.717_727del) is absent from gnomAD (gnomAD).

EPHB4 p.Cys239fs

c.717_727del · rs2485044907 · VCV2635609

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7.7	GERP 2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPHB4
Protein: p.Cys239fs
Coding: c.717_727del
MANE Select: NM_004444
dbSNP: rs2485044907
Type: Deletion
Location: chr7:100822352 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 239: 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.Arg240fs 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.Cys239Phe Uncertain significance ★ ⚠ same residue
EPHB4 p.Gln858fs Uncertain significance ★ same condition
EPHB4 p.Gly723fs Likely pathogenic 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-cys239fs (accessed [today's date]).

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