Is EBF3 p.Pro59Leu (c.176C>T) pathogenic?

EBF3 p.Pro59Leu (c.176C>T) is classified Uncertain significance in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). AlphaMissense: likely pathogenic (0.9986); No allele count reported in gnomAD v4.1 (AN 1,581,582); Associated with Inborn genetic diseases.

What condition is associated with EBF3 p.Pro59Leu (c.176C>T)?

EBF3 p.Pro59Leu (c.176C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EBF3 p.Pro59Leu (c.176C>T) in the general population?

EBF3 p.Pro59Leu (c.176C>T) is no allele count reported in gnomAD v4.1 (AN 1,581,582) (gnomAD).

What do computational predictors say about EBF3 p.Pro59Leu (c.176C>T)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

EBF3 p.Pro59Leu

c.176C>T · VCV3274351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,581,582)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic
REVEL	0.719	pathogenic-leaning
SaProt	LLR -14.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 4,677 bp · p 1e-06 · 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

No allele count reported in gnomAD v4.1 (AN 1,581,582). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EBF3
Protein: p.Pro59Leu
Coding: c.176C>T
MANE Select: NM_001375380
Type: single nucleotide variant
Location: chr10:129963482 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.89 · 2 PDB

Full EBF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBF3 p.Arg152Gly Pathogenic ★★ same condition
EBF3 p.Arg163Gln Pathogenic ★★ same condition
EBF3 p.Arg209Gln Pathogenic/Likely pathogenic ★★ same condition
EBF3 c.*9A>G Uncertain significance ★★ ⚠ same condition
EBF3 p.Asn100Asp Uncertain significance ★★ ⚠ same condition
EBF3 p.Asp286Asn Uncertain significance ★★ ⚠ same condition
EBF3 p.Gly291Arg Uncertain significance ★★ ⚠ same condition
EBF3 p.Thr33Ala Benign/Likely benign ★★ same condition

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/ebf3-p-pro59leu (accessed [today's date]).

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