Is EBF3 p.Ser555= (c.1665C>T) pathogenic?

EBF3 p.Ser555= (c.1665C>T) is classified Likely benign in EBF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Ultra-rare (popmax 0.0144%, amr); Associated with EBF3-related disorder.

What condition is associated with EBF3 p.Ser555= (c.1665C>T)?

EBF3 p.Ser555= (c.1665C>T) is associated with EBF3-related disorder (ClinVar).

How common is EBF3 p.Ser555= (c.1665C>T) in the general population?

EBF3 p.Ser555= (c.1665C>T) is ultra-rare (popmax 0.0144%, amr) (gnomAD).

EBF3 p.Ser555=

c.1665C>T · VCV3350667

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, amr)

Conditions

EBF3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.106	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.5	GERP -1.5, phastCons 0.97
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0144% Admixed American · 8/55,550 alleles

Filtering AF 0.00707% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00347% 55/1,583,974 alleles · ultra-rare exomes 54/1,431,696 · genomes 1/152,278 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0144%	6,944
East Asian	0.00917%	10,902
European (non-Finnish)	0.00343%	29,114
Remaining individualsnot grpmax-eligible	0.00326%	30,638
South Asian	0.00116%	86,576

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.Ser555=
Coding: c.1665C>T
MANE Select: NM_001375380
Type: single nucleotide variant
Location: chr10:129840339 (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

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-ser555 (accessed [today's date]).

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