Is BCL3 p.Leu82Phe (c.244C>T) pathogenic?

BCL3 p.Leu82Phe (c.244C>T) is classified Uncertain significance in BCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.1653); Ultra-rare (popmax 0.0123%, eas).

How common is BCL3 p.Leu82Phe (c.244C>T) in the general population?

BCL3 p.Leu82Phe (c.244C>T) is ultra-rare (popmax 0.0123%, eas) (gnomAD).

What do computational predictors say about BCL3 p.Leu82Phe (c.244C>T)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

BCL3 p.Leu82Phe

c.244C>T · rs373183384 · VCV2596040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0123%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.12	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 -0.04	GERP -3.2, phastCons 0.17
Regional constraint	o/e 0.95	unconstrained · MANE · 8,302 bp · p 0.39 · regional, not allelic
Overall
CADD	15.68	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 0.0123% East Asian · 4/32,464 alleles

Filtering AF 0.00417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00253%

Overall 0.00155% 21/1,353,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0218%	4,594
East Asiangrpmax	0.0123%	8,116
South Asian	0.00516%	19,382
European (non-Finnish)	0.000284%	351,917

Remaining individuals 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: BCL3
Protein: p.Leu82Phe
Coding: c.244C>T
MANE Select: NM_005178
dbSNP: rs373183384
Type: single nucleotide variant
Location: chr19:44749034 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 71.86 · 2 PDB

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

Similar variants

BCL3 p.Leu82Pro Uncertain significance ★ ⚠ same residue
BCL3 p.Leu82Val 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.Ala45Asp 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-leu82phe (accessed [today's date]).

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