Is EPHB4 p.Ala800fs (c.2397del) pathogenic?

EPHB4 p.Ala800fs (c.2397del) is classified Pathogenic in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-31). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with EPHB4 p.Ala800fs (c.2397del)?

EPHB4 p.Ala800fs (c.2397del) is associated with Cardiovascular phenotype (ClinVar).

How common is EPHB4 p.Ala800fs (c.2397del) in the general population?

EPHB4 p.Ala800fs (c.2397del) is absent from gnomAD (gnomAD).

EPHB4 p.Ala800fs

c.2397del · rs2485000821 · VCV1790636

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

Cardiovascular phenotype

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 6	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.Ala800fs
Coding: c.2397del
MANE Select: NM_004444
dbSNP: rs2485000821
Type: Deletion
Location: chr7:100806507 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 800: an α-helix; 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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPHB4 p.Ala800Thr Uncertain significance ★ ⚠ same residue
EPHB4 p.Gly975fs Uncertain significance ★ same condition
EPHB4 c.1870+5G>C Uncertain significance ★★ same condition
EPHB4 p.Ala262Val Uncertain significance ★★ ⚠ same condition
EPHB4 p.Ala345Gly Uncertain significance ★★ ⚠ same condition
EPHB4 p.Ala931Thr Uncertain significance ★★ ⚠ same condition
EPHB4 p.Arg148Trp Uncertain significance ★★ ⚠ same condition
EPHB4 p.Arg310Gln 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-ala800fs (accessed [today's date]).

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