Is EBF3 p.Arg129Pro (c.386G>C) pathogenic?

EBF3 p.Arg129Pro (c.386G>C) is classified Likely pathogenic in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-09). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EBF3 p.Arg129Pro (c.386G>C)?

EBF3 p.Arg129Pro (c.386G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EBF3 p.Arg129Pro (c.386G>C) in the general population?

EBF3 p.Arg129Pro (c.386G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBF3 p.Arg129Pro (c.386G>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

EBF3 p.Arg129Pro

c.386G>C · rs1859577030 · VCV985963

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar
REVEL	0.567	indeterminate
SaProt	LLR -11.99	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 4,677 bp · p 1e-06 · 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.Arg129Pro
Coding: c.386G>C
MANE Select: NM_001375380
dbSNP: rs1859577030
Type: single nucleotide variant
Location: chr10:129962196 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBF3 p.Arg152Gly Pathogenic ★★ same condition
EBF3 p.Arg163Gln Pathogenic ★★ same condition
EBF3 p.Arg209Gln Pathogenic/Likely pathogenic ★★ same condition
EBF3 c.*9A>G Uncertain significance ★★ ⚠ same condition
EBF3 p.Asn100Asp Uncertain significance ★★ ⚠ same condition
EBF3 p.Asp286Asn Uncertain significance ★★ ⚠ same condition
EBF3 p.Gly291Arg Uncertain significance ★★ ⚠ same condition
EBF3 p.Thr33Ala Benign/Likely benign ★★ 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-arg129pro (accessed [today's date]).

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