Is EPHB2 p.Tyr596= (c.1788C>T) pathogenic?

EPHB2 p.Tyr596= (c.1788C>T) is classified Likely benign in EPHB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-19). Ultra-rare (popmax 0.0583%, amr); Associated with EPHB2-related disorder.

What condition is associated with EPHB2 p.Tyr596= (c.1788C>T)?

EPHB2 p.Tyr596= (c.1788C>T) is associated with EPHB2-related disorder (ClinVar).

How common is EPHB2 p.Tyr596= (c.1788C>T) in the general population?

EPHB2 p.Tyr596= (c.1788C>T) is ultra-rare (popmax 0.0583%, amr) (gnomAD).

EPHB2 p.Tyr596=

c.1788C>T · rs142696573 · VCV3033967

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0583%, amr)

Conditions

EPHB2-related disorder

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 1.2	GERP 0.58, phastCons 1
Overall
CADD	8.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0583% Admixed American · 35/60,010 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00316% 51/1,614,098 alleles · ultra-rare exomes 32/1,461,892 · genomes 19/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0583%	1,715
Remaining individualsnot grpmax-eligible	0.0096%	10,415
African / African-American	0.00133%	74,922
European (non-Finnish)	0.000763%	131,117

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: EPHB2
Protein: p.Tyr596=
Coding: c.1788C>T
MANE Select: NM_017449
dbSNP: rs142696573
Type: single nucleotide variant
Location: chr1:22906009 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 5 PDB

Full EPHB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EPHB2-related disorder

Similar variants

EPHB2 p.Tyr240Asp Uncertain significance ⚠ same condition
EPHB2 c.968-7G>A Likely benign same condition
EPHB2 c.*120G>A Likely benign same condition
EPHB2 c.*213A>G Likely benign same condition
EPHB2 c.*291C>T Likely benign same condition
EPHB2 p.Asn755= Likely benign same condition
EPHB2 p.His583= Likely benign same condition
EPHB2 p.Phe803= Likely benign 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/ephb2-p-tyr596 (accessed [today's date]).

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