Is EBF3 p.Pro249= (c.747G>A) pathogenic?

EBF3 p.Pro249= (c.747G>A) is classified Likely benign in EBF3 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00344%, sas); Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with EBF3 p.Pro249= (c.747G>A)?

EBF3 p.Pro249= (c.747G>A) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is EBF3 p.Pro249= (c.747G>A) in the general population?

EBF3 p.Pro249= (c.747G>A) is very rare (popmax 0.00344%, sas) (gnomAD).

EBF3 p.Pro249=

c.747G>A · rs758276315 · VCV2681252

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00344%, sas)

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -3.7, phastCons 1
Overall
CADD	15.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00344% South Asian · 3/87,172 alleles

Filtering AF 0.000914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000454%

Overall 0.000947% 15/1,583,630 alleles · very rare exomes 14/1,431,356 · genomes 1/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00344%	29,057
Remaining individualsnot grpmax-eligible	0.00164%	61,060
Finnishnot grpmax-eligible	0.00157%	63,638
European (non-Finnish)	0.000861%	116,199

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.Pro249=
Coding: c.747G>A
MANE Select: NM_001375380
dbSNP: rs758276315
Type: single nucleotide variant
Location: chr10:129873486 (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

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

EBF3 p.Pro249Leu Uncertain significance ★ same residue
EBF3 p.Ala279fs Pathogenic ★★ same condition
EBF3 p.Leu154fs Likely pathogenic ★ same condition
EBF3 c.486-1G>A Pathogenic ★★ same type
EBF3 c.555-2A>G Likely pathogenic ★★ same type
EBF3 p.Arg152Gly Pathogenic ★★ same type
EBF3 p.Arg163Gln Pathogenic ★★ same type
EBF3 p.Arg163Leu Pathogenic ★★ 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/ebf3-p-pro249 (accessed [today's date]).

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