Is EBF3 p.Pro565Ser (c.1693C>T) pathogenic?

EBF3 p.Pro565Ser (c.1693C>T) is classified Uncertain significance in EBF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely pathogenic (0.9933); No allele count reported in gnomAD v4.1 (AN 1,591,132).

How common is EBF3 p.Pro565Ser (c.1693C>T) in the general population?

EBF3 p.Pro565Ser (c.1693C>T) is no allele count reported in gnomAD v4.1 (AN 1,591,132) (gnomAD).

What do computational predictors say about EBF3 p.Pro565Ser (c.1693C>T)?

AlphaMissense predicts likely pathogenic (score 0.9933) — an in-silico prediction, not a clinical call.

EBF3 p.Pro565Ser

c.1693C>T · VCV4088071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9933 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,132)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9933	likely pathogenic
REVEL	0.528	indeterminate
SaProt	LLR -12.56	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 10 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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 1,591,132). 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.Pro565Ser
Coding: c.1693C>T
MANE Select: NM_001375380
Type: single nucleotide variant
Location: chr10:129840311 (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

Similar variants

EBF3 p.Pro565= Benign/Likely benign ★★ same residue
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
EBF3 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same type
EBF3 p.Arg206Ter 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-pro565ser (accessed [today's date]).

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