Is EBF3 p.Phe2Leu (c.6T>G) pathogenic?

EBF3 p.Phe2Leu (c.6T>G) is classified Uncertain significance in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.9948); No allele count reported in gnomAD v4.1 (AN 1,519,574); Associated with Inborn genetic diseases.

What condition is associated with EBF3 p.Phe2Leu (c.6T>G)?

EBF3 p.Phe2Leu (c.6T>G) is associated with Inborn genetic diseases (ClinVar).

How common is EBF3 p.Phe2Leu (c.6T>G) in the general population?

EBF3 p.Phe2Leu (c.6T>G) is no allele count reported in gnomAD v4.1 (AN 1,519,574) (gnomAD).

What do computational predictors say about EBF3 p.Phe2Leu (c.6T>G)?

AlphaMissense predicts likely pathogenic (score 0.9948) — an in-silico prediction, not a clinical call.

EBF3 p.Phe2Leu

c.6T>G · rs1172759977 · VCV2324731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9948 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,519,574)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9948	likely pathogenic
REVEL	0.281	benign-leaning
SaProt	LLR -5.91	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 108 bp · p 0.2 · regional, not allelic
Overall
CADD	23.4	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

No allele count reported in gnomAD v4.1 (AN 1,519,574). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EBF3
Protein: p.Phe2Leu
Coding: c.6T>G
MANE Select: NM_001375380
dbSNP: rs1172759977
Type: single nucleotide variant
Location: chr10:129963763 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.89 · 2 PDB
Residue 2: the 'disordered' region

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-phe2leu (accessed [today's date]).

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