Is BCL3 p.Ala45Thr (c.133G>A) pathogenic?

BCL3 p.Ala45Thr (c.133G>A) is classified Uncertain significance in BCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.107); Rare (popmax 0.11%, afr).

How common is BCL3 p.Ala45Thr (c.133G>A) in the general population?

BCL3 p.Ala45Thr (c.133G>A) is rare (popmax 0.11%, afr) (gnomAD).

What do computational predictors say about BCL3 p.Ala45Thr (c.133G>A)?

AlphaMissense predicts likely benign (score 0.107) — an in-silico prediction, not a clinical call.

BCL3 p.Ala45Thr

c.133G>A · rs868370649 · VCV2392098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.107 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.107	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.41, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 8,302 bp · p 0.39 · regional, not allelic
Overall
CADD	18.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% African / African-American · 68/61,872 alleles

Filtering AF 0.0889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0812%

Overall 0.00628% 74/1,178,526 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.11%	910
Remaining individualsnot grpmax-eligible	0.00968%	10,331
Admixed American	0.00901%	11,094

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: BCL3
Protein: p.Ala45Thr
Coding: c.133G>A
MANE Select: NM_005178
dbSNP: rs868370649
Type: single nucleotide variant
Location: chr19:44748923 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 71.86 · 2 PDB
Residue 45: the 'disordered' region

Full BCL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL3 p.Ala45Asp Uncertain significance ★ ⚠ same residue
BCL3 p.Ala45Val Uncertain significance ★ ⚠ same residue
BCL3 p.Val258Met Uncertain significance ★★ same type
BCL3 p.Leu294= Benign ★★ same type
BCL3 p.Ala126Thr Uncertain significance ★ ⚠ same type
BCL3 p.Ala22Thr Uncertain significance ★ ⚠ same type
BCL3 p.Ala270Gly Uncertain significance ★ same type
BCL3 p.Ala46Ser 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/bcl3-p-ala45thr (accessed [today's date]).

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