Is BCL9 p.Met409Val (c.1225A>G) pathogenic?

BCL9 p.Met409Val (c.1225A>G) is classified Uncertain significance in BCL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.3543); Absent from gnomAD v4.1.

How common is BCL9 p.Met409Val (c.1225A>G) in the general population?

BCL9 p.Met409Val (c.1225A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL9 p.Met409Val (c.1225A>G)?

AlphaMissense predicts ambiguous (score 0.3543) — an in-silico prediction, not a clinical call.

BCL9 p.Met409Val

c.1225A>G · VCV4202354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3543 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3543	ambiguous
REVEL	0.537	indeterminate
SaProt	LLR -6.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,077 bp · p 0.29 · regional, not allelic
Overall
CADD	23.4	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.Met409Val
Coding: c.1225A>G
MANE Select: NM_004326
Type: single nucleotide variant
Location: chr1:147619380 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 43.07 · 8 PDB
Residue 409: the 'disordered' region

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-met409val (accessed [today's date]).

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