Is BCL3 p.Ile268Ser (c.803T>G) pathogenic?

BCL3 p.Ile268Ser (c.803T>G) is classified Uncertain significance in BCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-30). AlphaMissense: likely pathogenic (0.8177); Very rare (popmax 0.000257%, nfe).

How common is BCL3 p.Ile268Ser (c.803T>G) in the general population?

BCL3 p.Ile268Ser (c.803T>G) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about BCL3 p.Ile268Ser (c.803T>G)?

AlphaMissense predicts likely pathogenic (score 0.8177) — an in-silico prediction, not a clinical call.

BCL3 p.Ile268Ser

c.803T>G · rs2513620471 · VCV2688664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8177 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8177	likely pathogenic
REVEL	0.566	indeterminate
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 561 bp · p 0.72 · regional, not allelic
Overall
CADD	25.8	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 0.000257% European (non-Finnish) · 3/1,169,454 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000208% 3/1,441,580 alleles · very rare

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.Ile268Ser
Coding: c.803T>G
MANE Select: NM_005178
dbSNP: rs2513620471
Type: single nucleotide variant
Location: chr19:44757405 (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.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-ile268ser (accessed [today's date]).

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