Is BCL9 p.Arg485= (c.1455G>A) pathogenic?

BCL9 p.Arg485= (c.1455G>A) is classified Benign in BCL9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.6%, nfe).

How common is BCL9 p.Arg485= (c.1455G>A) in the general population?

BCL9 p.Arg485= (c.1455G>A) is low-frequency (popmax 1.6%, nfe) (gnomAD).

BCL9 p.Arg485=

c.1455G>A · rs80312516 · VCV777923

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.6%, nfe)

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 2.9	GERP 1.2, phastCons 1
Overall
CADD	7.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.6% European (non-Finnish) · 18,876/1,180,010 alleles

Filtering AF 1.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 1.3% 20,956/1,614,078 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.63%	38
European (non-Finnish)grpmax	1.6%	63
Remaining individualsnot grpmax-eligible	1.06%	94
Finnishnot grpmax-eligible	0.722%	139
Ashkenazi Jewishnot grpmax-eligible	0.699%	143
Admixed American	0.541%	185
African / African-American	0.245%	408
South Asian	0.228%	438
Middle Eastern	0.115%	866

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: BCL9
Protein: p.Arg485=
Coding: c.1455G>A
MANE Select: NM_004326
dbSNP: rs80312516
Type: single nucleotide variant
Location: chr1:147619610 (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.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
BCL9 p.Ala240Thr 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-arg485 (accessed [today's date]).

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