Is EBF4 p.Leu293Pro (c.878T>C) pathogenic?

EBF4 p.Leu293Pro (c.878T>C) is classified Uncertain significance in EBF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.5786); Absent from gnomAD v4.1.

How common is EBF4 p.Leu293Pro (c.878T>C) in the general population?

EBF4 p.Leu293Pro (c.878T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBF4 p.Leu293Pro (c.878T>C)?

AlphaMissense predicts likely pathogenic (score 0.5786) — an in-silico prediction, not a clinical call.

EBF4 p.Leu293Pro

c.878T>C · VCV4246264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5786 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5786	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -11.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 9,329 bp · p 0.2 · regional, not allelic
Overall
CADD	32.0	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: EBF4
Protein: p.Leu293Pro
Coding: c.878T>C
MANE Select: NM_001395167
Type: single nucleotide variant
Location: chr20:2749740 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.60
Residue 293: the ipt/tig domain

Full EBF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF4 p.Leu293Ile Uncertain significance ★ ⚠ same residue
EBF4 p.Arg164= Benign ★★ same type
EBF4 p.Ile91= Benign ★★ same type
EBF4 p.Ala102Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala102Val Uncertain significance ★ ⚠ same type
EBF4 p.Ala402Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala40Thr Uncertain significance ★ ⚠ same type
EBF4 p.Ala438Ser 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/ebf4-p-leu293pro (accessed [today's date]).

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