Is EBF3 p.Arg28Ser (c.82C>A) pathogenic?

EBF3 p.Arg28Ser (c.82C>A) is classified Uncertain significance in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-21). AlphaMissense: likely pathogenic (0.9823); No allele count reported in gnomAD v4.1 (AN 1,524,042); Associated with hypotonia, ataxia, and delayed development syndrome.

What condition is associated with EBF3 p.Arg28Ser (c.82C>A)?

EBF3 p.Arg28Ser (c.82C>A) is associated with hypotonia, ataxia, and delayed development syndrome (ClinVar).

How common is EBF3 p.Arg28Ser (c.82C>A) in the general population?

EBF3 p.Arg28Ser (c.82C>A) is no allele count reported in gnomAD v4.1 (AN 1,524,042) (gnomAD).

What do computational predictors say about EBF3 p.Arg28Ser (c.82C>A)?

AlphaMissense predicts likely pathogenic (score 0.9823) — an in-silico prediction, not a clinical call.

EBF3 p.Arg28Ser

c.82C>A · rs747420051 · VCV1032517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9823 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,524,042)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hypotonia, ataxia, and delayed development syndrome

Computational evidence

Protein change
AlphaMissense	0.9823	likely pathogenic
REVEL	0.383	indeterminate
SaProt	LLR -11.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.23	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP -1.6, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 108 bp · p 0.2 · regional, not allelic
Overall
CADD	34.0	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 1,524,042). 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.Arg28Ser
Coding: c.82C>A
MANE Select: NM_001375380
dbSNP: rs747420051
Type: single nucleotide variant
Location: chr10:129963687 (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 p.Arg28Pro Uncertain significance ★ ⚠ same residue
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.Arg206Ter Pathogenic ★★ same condition
EBF3 p.Arg209Gln Pathogenic/Likely 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-arg28ser (accessed [today's date]).

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