Is EPHB3 p.Pro438= (c.1314G>A) pathogenic?

EPHB3 p.Pro438= (c.1314G>A) is classified Benign in EPHB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-13). Common (popmax 8%, afr) — too common for a highly-penetrant pathogenic allele.

EPHB3 p.Pro438=

Q: How common is EPHB3 p.Pro438= (c.1314G>A) in the general population?

EPHB3 p.Pro438= (c.1314G>A) is common (popmax 8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1314G>A · rs34076689 · VCV767942

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8%, afr) — too common for a highly-penetrant pathogenic allele

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 -5.4
Overall
CADD	1.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8% African / African-American · 5,997/74,964 alleles

Filtering AF 7.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.76%

Overall 0.442% 7,115/1,608,730 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8%	13
Remaining individualsnot grpmax-eligible	0.492%	203
Admixed American	0.49%	204
Middle Eastern	0.331%	302
European (non-Finnish)	0.0411%	2,436
East Asian	0.0156%	6,399
South Asian	0.00991%	10,088

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: EPHB3
Protein: p.Pro438=
Coding: c.1314G>A
MANE Select: NM_004443
dbSNP: rs34076689
Type: single nucleotide variant
Location: chr3:184577143 (GRCh38)
Gene constraint: LOEUF 0.435 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.62 · 4 PDB
Residue 438: the fibronectin type-iii 1 domain

Full EPHB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHB3 c.1748+4C>T Benign ★★ same type
EPHB3 p.Phe689= Benign ★★ same type
EPHB3 p.Ala220Thr Uncertain significance ★ ⚠ same type
EPHB3 p.Ala229Val Uncertain significance ★ ⚠ same type
EPHB3 p.Ala315Thr Uncertain significance ★ ⚠ same type
EPHB3 p.Ala332Val Uncertain significance ★ ⚠ same type
EPHB3 p.Ala442Glu Uncertain significance ★ ⚠ same type
EPHB3 p.Ala517Thr Uncertain significance ★ ⚠ same type

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/ephb3-p-pro438 (accessed [today's date]).

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