Is EBF3 p.Arg206Ter (c.616C>T) pathogenic?

EBF3 p.Arg206Ter (c.616C>T) is classified Pathogenic in EBF3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Absent from gnomAD v4.1; Associated with hypotonia, ataxia, and delayed development syndrome.

How common is EBF3 p.Arg206Ter (c.616C>T) in the general population?

EBF3 p.Arg206Ter (c.616C>T) is absent from gnomAD v4.1 (gnomAD).

EBF3 p.Arg206Ter

Q: What condition is associated with EBF3 p.Arg206Ter (c.616C>T)?

EBF3 p.Arg206Ter (c.616C>T) is associated with hypotonia, ataxia, and delayed development syndrome, neurodevelopmental disorder (ClinVar).

c.616C>T · rs1057519522 · VCV375503

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.69, phastCons 1
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: EBF3
Protein: p.Arg206Ter
Coding: c.616C>T
MANE Select: NM_001375380
dbSNP: rs1057519522
Type: single nucleotide variant
Location: chr10:129877788 (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

Also linked: neurodevelopmental disorder

Similar variants

EBF3 c.486-1G>A Pathogenic ★★ same condition
EBF3 c.555-2A>G Likely pathogenic ★★ same condition
EBF3 p.Arg163Gln Pathogenic ★★ same condition
EBF3 p.Arg163Leu Pathogenic ★★ same condition
EBF3 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same condition
EBF3 p.Arg209Gln Pathogenic/Likely pathogenic ★★ same condition
EBF3 p.Arg209Trp Pathogenic/Likely pathogenic ★★ same condition
EBF3 p.Arg312Ter Pathogenic ★★ 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-arg206ter (accessed [today's date]).

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