Is EPHB2 p.Glu477Lys (c.1429G>A) pathogenic?

EPHB2 p.Glu477Lys (c.1429G>A) is classified Likely benign in EPHB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). AlphaMissense: likely benign (0.3077); Rare (popmax 0.32%, afr).

How common is EPHB2 p.Glu477Lys (c.1429G>A) in the general population?

EPHB2 p.Glu477Lys (c.1429G>A) is rare (popmax 0.32%, afr) (gnomAD).

What do computational predictors say about EPHB2 p.Glu477Lys (c.1429G>A)?

AlphaMissense predicts likely benign (score 0.3077) — an in-silico prediction, not a clinical call.

EPHB2 p.Glu477Lys

c.1429G>A · rs138075206 · VCV711269

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3077 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.32%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3077	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.55	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 203 kb · p 2.4e-23 · regional, not allelic
Overall
CADD	34.0	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 0.32% African / African-American · 240/75,056 alleles

Filtering AF 0.287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.274%

Overall 0.0167% 270/1,614,190 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.32%	313
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.0183%	5,456
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000254%	393,343

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.Glu477Lys
Coding: c.1429G>A
MANE Select: NM_017449
dbSNP: rs138075206
Type: single nucleotide variant
Location: chr1:22892884 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 5 PDB
Residue 477: the fibronectin type-iii 2 domain

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

Similar variants

EPHB2 p.Val414Ile Uncertain significance ★★ ⚠ same type
EPHB2 c.1766-9G>T Benign/Likely benign ★★ same type
EPHB2 p.Ala279Ser Benign ★★ same type
EPHB2 p.Asn242= Likely benign ★★ same type
EPHB2 p.Asp574= Benign ★★ same type
EPHB2 p.Asp678Asn Likely benign ★★ ⚠ same type
EPHB2 p.Gln875= Benign ★★ same type
EPHB2 p.Ser170= 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-glu477lys (accessed [today's date]).

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