Is EPHB2 p.Asp678Asn (c.2032G>A) pathogenic?

EPHB2 p.Asp678Asn (c.2032G>A) is classified Likely benign in EPHB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-11-22). AlphaMissense: likely benign (0.1837); Rare (popmax 0.658%, nfe); Associated with prostate cancer/brain cancer susceptibility.

What condition is associated with EPHB2 p.Asp678Asn (c.2032G>A)?

EPHB2 p.Asp678Asn (c.2032G>A) is associated with prostate cancer/brain cancer susceptibility (ClinVar).

How common is EPHB2 p.Asp678Asn (c.2032G>A) in the general population?

EPHB2 p.Asp678Asn (c.2032G>A) is rare (popmax 0.658%, nfe) (gnomAD).

What do computational predictors say about EPHB2 p.Asp678Asn (c.2032G>A)?

AlphaMissense predicts likely benign (score 0.1837) — an in-silico prediction, not a clinical call.

EPHB2 p.Asp678Asn

c.2032G>A · rs28936395 · VCV8534

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1837 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.658%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

prostate cancer/brain cancer susceptibility

Computational evidence

Protein change
AlphaMissense	0.1837	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 203 kb · p 2.4e-23 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.658% European (non-Finnish) · 7,760/1,180,034 alleles

Filtering AF 0.645% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.64%

Overall 0.535% 8,643/1,614,172 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.658%	152
Remaining individualsnot grpmax-eligible	0.518%	193
Ashkenazi Jewishnot grpmax-eligible	0.257%	390
Finnishnot grpmax-eligible	0.223%	448
Admixed American	0.217%	462
South Asian	0.144%	695
African / African-American	0.103%	974
Middle Eastern	0.0165%	6,062
East Asian	0.00223%	44,880

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.Asp678Asn
Coding: c.2032G>A
MANE Select: NM_017449
dbSNP: rs28936395
Type: single nucleotide variant
Location: chr1:22906853 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 5 PDB
Residue 678: the protein kinase domain; a UniProt-annotated variant site (in)

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

Disease context

prostate cancer/brain cancer susceptibility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPHB2 p.Asp678Glu Uncertain significance ★ ⚠ same residue
EPHB2 p.Asp678Gly Uncertain significance ★ ⚠ same residue
EPHB2 p.Ala279Ser Benign ★★ same condition
EPHB2 p.Gln722Ter Pathogenic same condition
EPHB2 c.*214_*215del Uncertain significance ★ same condition
EPHB2 p.Val414Ile Uncertain significance ★★ ⚠ same type
EPHB2 c.1766-9G>T Benign/Likely benign ★★ same type
EPHB2 p.Asn242= Likely benign ★★ 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/ephb2-p-asp678asn (accessed [today's date]).

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