Is EBF2 p.Arg128Ser (c.384G>C) pathogenic?

EBF2 p.Arg128Ser (c.384G>C) is classified Uncertain significance in EBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1.

How common is EBF2 p.Arg128Ser (c.384G>C) in the general population?

EBF2 p.Arg128Ser (c.384G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBF2 p.Arg128Ser (c.384G>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

EBF2 p.Arg128Ser

c.384G>C · VCV3843241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 9% in EBF2
REVEL	0.537	indeterminate
SaProt	LLR -10.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.09	GERP -3.9, phastCons 0.92
Regional constraint	o/e 0.68	unconstrained · MANE · 178 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	23.2	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

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: EBF2
Protein: p.Arg128Ser
Coding: c.384G>C
MANE Select: NM_022659
Type: single nucleotide variant
Location: chr8:26040640 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.38

Full EBF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF2 c.1164+4A>G Benign ★★ same type
EBF2 p.Lys352= Benign ★★ same type
EBF2 p.Ala420Thr Uncertain significance ★ ⚠ same type
EBF2 p.Ala47Gly Uncertain significance ★ ⚠ same type
EBF2 p.Ala47Ser Uncertain significance ★ ⚠ same type
EBF2 p.Ala555Thr Uncertain significance ★ ⚠ same type
EBF2 p.Ala87Thr Uncertain significance ★ ⚠ same type
EBF2 p.Arg205Met Uncertain significance ★ ⚠ same type

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/ebf2-p-arg128ser (accessed [today's date]).

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