Is EPHB4 p.Gly104= (c.312G>A) pathogenic?

EPHB4 p.Gly104= (c.312G>A) is classified Likely benign in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EPHB4 p.Gly104= (c.312G>A)?

EPHB4 p.Gly104= (c.312G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is EPHB4 p.Gly104= (c.312G>A) in the general population?

EPHB4 p.Gly104= (c.312G>A) is absent from gnomAD v4.1 (gnomAD).

EPHB4 p.Gly104=

c.312G>A · rs1471305443 · VCV3224289

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.49	GERP -4.2, phastCons 0.012
Overall
CADD	1.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPHB4
Protein: p.Gly104=
Coding: c.312G>A
MANE Select: NM_004444
dbSNP: rs1471305443
Type: single nucleotide variant
Location: chr7:100823743 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB
Residue 104: a disulfide bond; the eph lbd 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-gly104 (accessed [today's date]).

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