Is BCL9 p.Pro766= (c.2298A>G) pathogenic?

BCL9 p.Pro766= (c.2298A>G) is classified Likely benign in BCL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Ultra-rare (popmax 0.056%, afr).

How common is BCL9 p.Pro766= (c.2298A>G) in the general population?

BCL9 p.Pro766= (c.2298A>G) is ultra-rare (popmax 0.056%, afr) (gnomAD).

BCL9 p.Pro766=

c.2298A>G · rs369043753 · VCV745937

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, afr)

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 -0.39	GERP -4.5, phastCons 0.004
Overall
CADD	5.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% African / African-American · 42/75,030 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00322% 52/1,614,064 alleles · ultra-rare exomes 26/1,461,810 · genomes 26/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.056%	1,786
Admixed American	0.00667%	15,003
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.000169%	589,991

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: BCL9
Protein: p.Pro766=
Coding: c.2298A>G
MANE Select: NM_004326
dbSNP: rs369043753
Type: single nucleotide variant
Location: chr1:147620453 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 43.07 · 8 PDB

Full BCL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL9 c.661-8G>T Benign/Likely benign ★★ same type
BCL9 p.Arg485= Benign ★★ same type
BCL9 p.Ala1042Thr Uncertain significance ★ ⚠ same type
BCL9 p.Ala1190Val Uncertain significance ★ ⚠ same type
BCL9 p.Ala1281Asp Uncertain significance ★ ⚠ same type
BCL9 p.Ala128Pro Uncertain significance ★ ⚠ same type
BCL9 p.Ala1337Val Uncertain significance ★ ⚠ same type
BCL9 p.Ala1407Gly Uncertain significance ★ ⚠ 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/bcl9-p-pro766 (accessed [today's date]).

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