Is EPHB4 p.Asp385fs (c.1153dup) pathogenic?

EPHB4 p.Asp385fs (c.1153dup) is classified Likely pathogenic in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-10). Ultra-rare (gnomAD MAF 1.68e-06); Associated with capillary malformation-arteriovenous malformation 2.

What condition is associated with EPHB4 p.Asp385fs (c.1153dup)?

EPHB4 p.Asp385fs (c.1153dup) is associated with capillary malformation-arteriovenous malformation 2 (ClinVar).

How common is EPHB4 p.Asp385fs (c.1153dup) in the general population?

EPHB4 p.Asp385fs (c.1153dup) is ultra-rare (gnomAD MAF 1.68e-06) (gnomAD).

EPHB4 p.Asp385fs

c.1153dup · rs761905713 · VCV1678612

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.68e-06)

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 6 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP -0.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000168% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: EPHB4
Protein: p.Asp385fs
Coding: c.1153dup
MANE Select: NM_004444
dbSNP: rs761905713
Type: Duplication
Location: chr7:100819700 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 385: a UniProt-annotated variant site (in cmavm2); the fibronectin type-iii 1 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 p.Leu347fs Pathogenic ★★ same condition
EPHB4 c.2484+2dup Likely pathogenic ★ same condition
EPHB4 p.Asp376fs Likely pathogenic ★ same condition
EPHB4 p.Asp758fs Likely pathogenic ★ same condition
EPHB4 p.Glu388fs Likely pathogenic ★ same condition
EPHB4 p.Gly622fs Likely pathogenic ★ same condition
EPHB4 p.Leu12fs Pathogenic ★ same condition
EPHB4 p.Trp245fs 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-asp385fs (accessed [today's date]).

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