Is EBF3 p.Val486fs (c.1457_1460del) pathogenic?

EBF3 p.Val486fs (c.14571460del) is classified Uncertain significance in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). Very rare (popmax 8.47e-05%, nfe); Associated with EBF3-related disorder.

What condition is associated with EBF3 p.Val486fs (c.1457_1460del)?

EBF3 p.Val486fs (c.1457_1460del) is associated with EBF3-related disorder (ClinVar).

How common is EBF3 p.Val486fs (c.1457_1460del) in the general population?

EBF3 p.Val486fs (c.1457_1460del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EBF3 p.Val486fs

c.1457_1460del · rs2493746916 · VCV2637393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

EBF3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP -0.79, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,613,900 alleles · very rare exomes 1/1,461,884 · genomes 0/152,016 · joint denominator

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: EBF3
Protein: p.Val486fs
Coding: c.1457_1460del
MANE Select: NM_001375380
dbSNP: rs2493746916
Type: Deletion
Location: chr10:129840945 (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

EBF3-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBF3 p.Asn40fs Likely pathogenic ★ same condition
EBF3 c.1040-7del Likely benign same condition
EBF3 p.Arg404Ter Pathogenic/Likely pathogenic ★★ same condition
EBF3 c.1194+1G>C Likely pathogenic ★ same condition
EBF3 p.Arg163Pro Likely pathogenic ★ same condition
EBF3 p.Cys161Arg Likely pathogenic ★ same condition
EBF3 p.Met232Lys Likely pathogenic ★ same condition
EBF3 p.Val82Met Uncertain significance ★ ⚠ 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-val486fs (accessed [today's date]).

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