Is EPHB4 p.Pro231= (c.693T>C) pathogenic?

EPHB4 p.Pro231= (c.693T>C) is classified Likely benign in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-18). No allele count reported in gnomAD v4.1 (AN 1,571,014); Associated with Cardiovascular phenotype.

What condition is associated with EPHB4 p.Pro231= (c.693T>C)?

EPHB4 p.Pro231= (c.693T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is EPHB4 p.Pro231= (c.693T>C) in the general population?

EPHB4 p.Pro231= (c.693T>C) is no allele count reported in gnomAD v4.1 (AN 1,571,014) (gnomAD).

EPHB4 p.Pro231=

c.693T>C · rs2485045056 · VCV1756256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,014)

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 -10	GERP -4.7
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,571,014). 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.Pro231=
Coding: c.693T>C
MANE Select: NM_004444
dbSNP: rs2485045056
Type: single nucleotide variant
Location: chr7:100822386 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 231: a UniProt-annotated variant site (in cmavm2)

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.Pro231Ser Benign/Likely benign ★★ same residue
EPHB4 p.Pro231Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
EPHB4 p.Pro231Leu Uncertain significance ★ ⚠ 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

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-pro231 (accessed [today's date]).

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