Is BCL9 p.Glu650Val (c.1949A>T) pathogenic?

BCL9 p.Glu650Val (c.1949A>T) is classified Uncertain significance in BCL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely pathogenic (0.7267); Absent from gnomAD v4.1.

How common is BCL9 p.Glu650Val (c.1949A>T) in the general population?

BCL9 p.Glu650Val (c.1949A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL9 p.Glu650Val (c.1949A>T)?

AlphaMissense predicts likely pathogenic (score 0.7267) — an in-silico prediction, not a clinical call.

BCL9 p.Glu650Val

c.1949A>T · VCV3260678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7267 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7267	likely pathogenic
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP -0.39, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,077 bp · p 0.29 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCL9
Protein: p.Glu650Val
Coding: c.1949A>T
MANE Select: NM_004326
Type: single nucleotide variant
Location: chr1:147620104 (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-glu650val (accessed [today's date]).

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