Is EBF3 p.Asp222fs (c.663_685del) pathogenic?

EBF3 p.Asp222fs (c.663685del) is classified Likely pathogenic in EBF3 (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with hypotonia, ataxia, and delayed development syndrome.

What condition is associated with EBF3 p.Asp222fs (c.663_685del)?

EBF3 p.Asp222fs (c.663_685del) is associated with hypotonia, ataxia, and delayed development syndrome (ClinVar).

How common is EBF3 p.Asp222fs (c.663_685del) in the general population?

EBF3 p.Asp222fs (c.663_685del) is no gnomAD frequency available for this variant (gnomAD).

EBF3 p.Asp222fs

c.663_685del · rs2494042652 · VCV3024299

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypotonia, ataxia, and delayed development syndrome

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 8 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Asp222fs
Coding: c.663_685del
MANE Select: NM_001375380
dbSNP: rs2494042652
Type: Deletion
Location: chr10:129873548 (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

hypotonia, ataxia, and delayed development syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBF3 c.485+2_485+8del Pathogenic/Likely pathogenic ★★ same condition
EBF3 p.Thr477fs Pathogenic ★★ same condition
EBF3 c.291+2del Pathogenic ★ same condition
EBF3 p.Ile183fs Likely pathogenic ★ same condition
EBF3 p.Leu192del Likely pathogenic ★ same condition
EBF3 p.Met232fs Likely pathogenic ★ same condition
EBF3 p.Thr122fs Likely pathogenic ★ same condition
EBF3 c.636+19del 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-asp222fs (accessed [today's date]).

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