Is EPHB4 p.Gln851Pro (c.2552_2553delinsCC) pathogenic?

EPHB4 p.Gln851Pro (c.25522553delinsCC) is classified Uncertain significance in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). Absent from gnomAD.

How common is EPHB4 p.Gln851Pro (c.2552_2553delinsCC) in the general population?

EPHB4 p.Gln851Pro (c.2552_2553delinsCC) is absent from gnomAD (gnomAD).

EPHB4 p.Gln851Pro

c.2552_2553delinsCC · rs2484998001 · VCV2818477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,002 bp · p 0.042 · regional, not allelic

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.Gln851Pro
Coding: c.2552_2553delinsCC
MANE Select: NM_004444
dbSNP: rs2484998001
Type: Indel
Location: chr7:100805626 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 851: 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

Similar variants

EPHB4 p.Glu154fs Likely pathogenic ★ same type
EPHB4 p.Lys616fs Likely pathogenic ★ same type
EPHB4 c.52+14_52+15delinsGC Uncertain significance ★ same type
EPHB4 p.Arg206Leu Uncertain significance ★ same type
EPHB4 p.Cys253Ser Uncertain significance ★ 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-gln851pro (accessed [today's date]).

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