Is EPHB4 p.Ala14= (c.42A>G) pathogenic?

EPHB4 p.Ala14= (c.42A>G) is classified Likely benign in EPHB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). Very rare (popmax 0.00547%, afr); Associated with Cardiovascular phenotype.

What condition is associated with EPHB4 p.Ala14= (c.42A>G)?

EPHB4 p.Ala14= (c.42A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is EPHB4 p.Ala14= (c.42A>G) in the general population?

EPHB4 p.Ala14= (c.42A>G) is very rare (popmax 0.00547%, afr) (gnomAD).

EPHB4 p.Ala14=

c.42A>G · rs1010329048 · VCV2565141

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00547%, afr)

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 -0.86	GERP -3.6
Overall
CADD	4.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00547% African / African-American · 4/73,072 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000383% 6/1,565,192 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00547%	18,268
East Asian	0.00243%	41,192
South Asian	0.00117%	85,658

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.Ala14=
Coding: c.42A>G
MANE Select: NM_004444
dbSNP: rs1010329048
Type: single nucleotide variant
Location: chr7:100826989 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 23 PDB

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.Ala14Thr Benign/Likely benign ★★ ⚠ same residue
EPHB4 p.Ala14Val 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
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-ala14 (accessed [today's date]).

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