Is EBF3 p.Pro565= (c.1695C>T) pathogenic?

EBF3 p.Pro565= (c.1695C>T) is classified Benign/Likely benign in EBF3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Rare (popmax 0.223%, nfe).

How common is EBF3 p.Pro565= (c.1695C>T) in the general population?

EBF3 p.Pro565= (c.1695C>T) is rare (popmax 0.223%, nfe) (gnomAD).

EBF3 p.Pro565=

c.1695C>T · rs148512369 · VCV789310

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.223%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.025	GERP -5.7, phastCons 0.51
Overall
CADD	10.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.223% European (non-Finnish) · 2,607/1,169,286 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.213%

Overall 0.174% 2,771/1,591,842 alleles · rare exomes 2,589/1,439,480 · genomes 182/152,362 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)grpmax	0.223%	449
Remaining individualsnot grpmax-eligible	0.12%	833
Admixed American	0.0494%	2,025
East Asian	0.0364%	2,745
African / African-American	0.0321%	3,116
Middle Eastern	0.0166%	6,020
Ashkenazi Jewishnot grpmax-eligible	0.0137%	7,278
Finnishnot grpmax-eligible	0.0113%	8,877
South Asian	0.00802%	12,475

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro565=
Coding: c.1695C>T
MANE Select: NM_001375380
dbSNP: rs148512369
Type: single nucleotide variant
Location: chr10:129840309 (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.Pro565Ser Uncertain significance ★ ⚠ 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-pro565 (accessed [today's date]).

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