Is EBF3 p.Arg152Cys (c.454C>T) pathogenic?

EBF3 p.Arg152Cys (c.454C>T) is classified Likely pathogenic in EBF3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-07). AlphaMissense: likely pathogenic (0.9983); Absent from gnomAD v4.1; Associated with hypotonia, ataxia, and delayed development syndrome.

What condition is associated with EBF3 p.Arg152Cys (c.454C>T)?

EBF3 p.Arg152Cys (c.454C>T) is associated with hypotonia, ataxia, and delayed development syndrome (ClinVar).

How common is EBF3 p.Arg152Cys (c.454C>T) in the general population?

EBF3 p.Arg152Cys (c.454C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBF3 p.Arg152Cys (c.454C>T)?

AlphaMissense predicts likely pathogenic (score 0.9983) — an in-silico prediction, not a clinical call.

EBF3 p.Arg152Cys

c.454C>T · rs2134623972 · VCV1701824

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hypotonia, ataxia, and delayed development syndrome

Computational evidence

Protein change
AlphaMissense	0.9983	likely pathogenic ✓ concordant with ClinVar
REVEL	0.607	indeterminate
SaProt	LLR -16.88	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.3, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 85 kb · p 4.3e-15 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg152Cys
Coding: c.454C>T
MANE Select: NM_001375380
dbSNP: rs2134623972
Type: single nucleotide variant
Location: chr10:129958965 (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.Arg152Leu Pathogenic ★ same residue
EBF3 p.Arg152Pro Likely pathogenic ★ same residue
EBF3 p.Arg152Gly Pathogenic ★★ 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

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-arg152cys (accessed [today's date]).

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