Is EPHB4 p.Glu890Asp (c.2670G>T) pathogenic?

EPHB4 p.Glu890Asp (c.2670G>T) is classified Benign/Likely benign in EPHB4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0643); Rare (popmax 0.914%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EPHB4 p.Glu890Asp (c.2670G>T)?

EPHB4 p.Glu890Asp (c.2670G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is EPHB4 p.Glu890Asp (c.2670G>T) in the general population?

EPHB4 p.Glu890Asp (c.2670G>T) is rare (popmax 0.914%, nfe) (gnomAD).

What do computational predictors say about EPHB4 p.Glu890Asp (c.2670G>T)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

EPHB4 p.Glu890Asp

c.2670G>T · rs35638378 · VCV774194

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.914%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.27, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 3,002 bp · p 0.042 · regional, not allelic
Overall
CADD	16.46	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.914% European (non-Finnish) · 10,372/1,134,394 alleles

Filtering AF 0.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.894%

Overall 0.754% 11,473/1,521,620 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.914%	109
Remaining individualsnot grpmax-eligible	0.673%	149
Amishnot grpmax-eligible	0.439%	228
Admixed American	0.434%	230
Ashkenazi Jewishnot grpmax-eligible	0.342%	293
Middle Eastern	0.289%	346
South Asian	0.236%	424
Finnishnot grpmax-eligible	0.172%	580
African / African-American	0.172%	581

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: EPHB4
Protein: p.Glu890Asp
Coding: c.2670G>T
MANE Select: NM_004444
dbSNP: rs35638378
Type: single nucleotide variant
Location: chr7:100805509 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 890: a UniProt-annotated variant site (in cmavm2); the protein kinase domain; a UniProt-annotated variant site (in)

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.Glu890Gln Uncertain significance ★ ⚠ same residue
EPHB4 p.Glu890= Likely benign ★ same residue
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-glu890asp (accessed [today's date]).

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