Is EPHB1 p.Val817Asp (c.2450T>A) pathogenic?

EPHB1 p.Val817Asp (c.2450T>A) is classified Uncertain significance in EPHB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1.

How common is EPHB1 p.Val817Asp (c.2450T>A) in the general population?

EPHB1 p.Val817Asp (c.2450T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHB1 p.Val817Asp (c.2450T>A)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

EPHB1 p.Val817Asp

c.2450T>A · VCV4664780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -17.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 463 kb · p 2.5e-12 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPHB1
Protein: p.Val817Asp
Coding: c.2450T>A
MANE Select: NM_004441
Type: single nucleotide variant
Location: chr3:135241251 (GRCh38)
Gene constraint: LOEUF 0.441 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.95 · 8 PDB
Residue 817: an α-helix; the protein kinase domain

Full EPHB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHB1 p.Ile561= Benign ★★ same type
EPHB1 p.Phe552= Benign/Likely benign ★★ same type
EPHB1 p.Thr981= Benign ★★ same type
EPHB1 c.2347-1G>A Uncertain significance ★ same type
EPHB1 p.Ala12Ser Uncertain significance ★ ⚠ same type
EPHB1 p.Ala132Gly Uncertain significance ★ ⚠ same type
EPHB1 p.Ala182Thr Uncertain significance ★ ⚠ same type
EPHB1 p.Ala39Val 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/ephb1-p-val817asp (accessed [today's date]).

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