Is EPHB4 p.Ser799= (c.2397C>T) pathogenic?

EPHB4 p.Ser799= (c.2397C>T) is classified Benign/Likely benign in EPHB4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-13). Rare (popmax 0.115%, mid); Associated with Cardiovascular phenotype.

What condition is associated with EPHB4 p.Ser799= (c.2397C>T)?

EPHB4 p.Ser799= (c.2397C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is EPHB4 p.Ser799= (c.2397C>T) in the general population?

EPHB4 p.Ser799= (c.2397C>T) is rare (popmax 0.115%, mid) (gnomAD).

EPHB4 p.Ser799=

c.2397C>T · rs201140601 · VCV1790635

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -5
Overall
CADD	5.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0159% 256/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
European (non-Finnish)	0.0186%	5,364
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.01%	9,998
African / African-American	0.00933%	10,716
East Asian	0.00446%	22,431
South Asian	0.00329%	30,363
Finnishnot grpmax-eligible	0.00156%	64,022

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.Ser799=
Coding: c.2397C>T
MANE Select: NM_004444
dbSNP: rs201140601
Type: single nucleotide variant
Location: chr7:100806507 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 799: 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 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
EPHB4 p.Arg483Gln Uncertain significance ★★ ⚠ same condition
EPHB4 p.Arg499Gln 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-ser799 (accessed [today's date]).

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