Is EPHA4 p.Arg890del (c.2669_2671del) pathogenic?

EPHA4 p.Arg890del (c.26692671del) is classified Uncertain significance in EPHA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). Very rare (popmax 0.000169%, nfe).

How common is EPHA4 p.Arg890del (c.2669_2671del) in the general population?

EPHA4 p.Arg890del (c.2669_2671del) is very rare (popmax 0.000169%, nfe) (gnomAD).

EPHA4 p.Arg890del

c.2669_2671del · VCV4742423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 10	GERP 2.3, phastCons 1
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,000 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,946 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EPHA4
Protein: p.Arg890del
Coding: c.2669_2671del
MANE Select: NM_004438
Type: Deletion
Location: chr2:221429977 (GRCh38)
Gene constraint: LOEUF 0.256 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.93 · 17 PDB

Full EPHA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA4 p.Arg890Thr Uncertain significance ★ ⚠ same residue
EPHA4 p.Ala912fs Uncertain significance ★ same type
EPHA4 c.1775-16_1775-14del Likely benign ★ 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/epha4-p-arg890del (accessed [today's date]).

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