Is EPHB4 p.Phe518fs (c.1548del) pathogenic?

EPHB4 p.Phe518fs (c.1548del) is classified Pathogenic in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-20). Absent from gnomAD.

How common is EPHB4 p.Phe518fs (c.1548del) in the general population?

EPHB4 p.Phe518fs (c.1548del) is absent from gnomAD (gnomAD).

EPHB4 p.Phe518fs

c.1548del · rs2485028164 · VCV2020695

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

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 8 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	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.Phe518fs
Coding: c.1548del
MANE Select: NM_004444
dbSNP: rs2485028164
Type: Deletion
Location: chr7:100817232 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 518: an α-helix; a UniProt-annotated variant site (in cmavm2); the fibronectin type-iii 2 domain

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

Similar variants

EPHB4 c.124-11_124-9del Uncertain significance ★★ same type
EPHB4 c.52+14_52+15del Benign ★★ same type
EPHB4 c.52+14del Benign ★★ same type
EPHB4 c.1691_1691+10del Likely pathogenic ★ same type
EPHB4 c.50_52+2del Likely pathogenic ★ same type
EPHB4 p.Ala153fs Pathogenic ★ same type
EPHB4 p.Ala476fs Likely pathogenic ★ same type
EPHB4 p.Ala800fs Pathogenic ★ same type

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-phe518fs (accessed [today's date]).

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