Is EPHB4 p.Phe797fs (c.2389_2392del) pathogenic?

EPHB4 p.Phe797fs (c.23892392del) is classified Pathogenic in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). Absent from gnomAD; Associated with capillary malformation-arteriovenous malformation 2.

What condition is associated with EPHB4 p.Phe797fs (c.2389_2392del)?

EPHB4 p.Phe797fs (c.2389_2392del) is associated with capillary malformation-arteriovenous malformation 2 (ClinVar).

How common is EPHB4 p.Phe797fs (c.2389_2392del) in the general population?

EPHB4 p.Phe797fs (c.2389_2392del) is absent from gnomAD (gnomAD).

EPHB4 p.Phe797fs

c.2389_2392del · rs2485000836 · VCV3255221

Pathogenic Single submitter

Classification

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

capillary malformation-arteriovenous malformation 2

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 14 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.5, 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.Phe797fs
Coding: c.2389_2392del
MANE Select: NM_004444
dbSNP: rs2485000836
Type: Deletion
Location: chr7:100806512 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 797: a UniProt-annotated variant site (in cmavm2); the protein kinase domain

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

Disease context

capillary malformation-arteriovenous malformation 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Leu347fs Pathogenic ★★ same condition
EPHB4 p.Trp72Ter Pathogenic/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-phe797fs (accessed [today's date]).

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