Is EBF3 p.Pro263= (c.789G>A) pathogenic?

EBF3 p.Pro263= (c.789G>A) is classified Likely benign in EBF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-31). Ultra-rare (popmax 0.0329%, mid); Associated with EBF3-related disorder.

What condition is associated with EBF3 p.Pro263= (c.789G>A)?

EBF3 p.Pro263= (c.789G>A) is associated with EBF3-related disorder (ClinVar).

How common is EBF3 p.Pro263= (c.789G>A) in the general population?

EBF3 p.Pro263= (c.789G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

EBF3 p.Pro263=

c.789G>A · VCV3350743

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

EBF3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.8	GERP -3.7
Overall
CADD	8.763	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00465% 75/1,613,996 alleles · ultra-rare exomes 65/1,461,760 · genomes 10/152,236 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.00667%	14,991
European (non-Finnish)	0.00525%	19,032
East Asian	0.00446%	22,439
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0022%	45,543

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EBF3
Protein: p.Pro263=
Coding: c.789G>A
MANE Select: NM_001375380
Type: single nucleotide variant
Location: chr10:129867905 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.89 · 2 PDB
Residue 263: the ipt/tig domain

Full EBF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EBF3-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EBF3 p.Arg404Ter Pathogenic/Likely pathogenic ★★ same condition
EBF3 c.1194+1G>C Likely pathogenic ★ same condition
EBF3 p.Arg163Pro Likely pathogenic ★ same condition
EBF3 p.Cys161Arg Likely pathogenic ★ same condition
EBF3 p.Met232Lys Likely pathogenic ★ same condition
EBF3 p.Val82Met Uncertain significance ★ ⚠ same condition
EBF3 c.1373-10A>G Likely benign same condition
EBF3 c.412-7C>T 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-pro263 (accessed [today's date]).

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