Is EPHA3 p.Ile882Phe (c.2644A>T) pathogenic?

EPHA3 p.Ile882Phe (c.2644A>T) is classified Uncertain significance in EPHA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: likely pathogenic (0.8779); Absent from gnomAD v4.1.

How common is EPHA3 p.Ile882Phe (c.2644A>T) in the general population?

EPHA3 p.Ile882Phe (c.2644A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHA3 p.Ile882Phe (c.2644A>T)?

AlphaMissense predicts likely pathogenic (score 0.8779) — an in-silico prediction, not a clinical call.

EPHA3 p.Ile882Phe

c.2644A>T · VCV3275914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8779 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8779	likely pathogenic
REVEL	0.431	indeterminate
SaProt	LLR -12.70	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 372 kb · p 0.42 · regional, not allelic
Overall
CADD	28.3	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: EPHA3
Protein: p.Ile882Phe
Coding: c.2644A>T
MANE Select: NM_005233
Type: single nucleotide variant
Location: chr3:89450324 (GRCh38)
Gene constraint: LOEUF 0.508 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 81.22 · 28 PDB
Residue 882: the protein kinase domain; an α-helix

Full EPHA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA3 p.Ala777Gly Benign ★★ ⚠ same type
EPHA3 p.Val597Ile Likely benign ★★ same type
EPHA3 p.Ala182Val Uncertain significance ★ ⚠ same type
EPHA3 p.Ala427Val Uncertain significance ★ ⚠ same type
EPHA3 p.Ala546Thr Uncertain significance ★ ⚠ same type
EPHA3 p.Ala550Pro Uncertain significance ★ ⚠ same type
EPHA3 p.Ala895Val Uncertain significance ★ ⚠ same type
EPHA3 p.Arg312Trp 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/epha3-p-ile882phe (accessed [today's date]).

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