Is BCL3 p.Val248Met (c.742G>A) pathogenic?

BCL3 p.Val248Met (c.742G>A) is classified Uncertain significance in BCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: ambiguous (0.4106); Very rare (popmax 0.00134%, afr).

How common is BCL3 p.Val248Met (c.742G>A) in the general population?

BCL3 p.Val248Met (c.742G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about BCL3 p.Val248Met (c.742G>A)?

AlphaMissense predicts ambiguous (score 0.4106) — an in-silico prediction, not a clinical call.

BCL3 p.Val248Met

c.742G>A · VCV3480160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.4106	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -8.19	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.93, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 561 bp · p 0.72 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.00134% African / African-American · 1/74,738 alleles

Overall 0.000138% 2/1,453,462 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,738
European (non-Finnish)	8.5e-05%	1,176,347

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.Val248Met
Coding: c.742G>A
MANE Select: NM_005178
Type: single nucleotide variant
Location: chr19:44757344 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 71.86 · 2 PDB
Residue 248: an α-helix

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

Similar variants

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
BCL3 p.Ala45Thr Uncertain significance ★ ⚠ same type
BCL3 p.Ala45Val 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-val248met (accessed [today's date]).

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