Is BCL3 p.Pro418Ala (c.1252C>G) pathogenic?

BCL3 p.Pro418Ala (c.1252C>G) is classified Uncertain significance in BCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.0632); Absent from gnomAD v4.1.

How common is BCL3 p.Pro418Ala (c.1252C>G) in the general population?

BCL3 p.Pro418Ala (c.1252C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL3 p.Pro418Ala (c.1252C>G)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

BCL3 p.Pro418Ala

c.1252C>G · rs1967380597 · VCV2546951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.33	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 0.61	GERP 0.98, phastCons 0.006
Regional constraint	o/e 1.09	unconstrained · MANE · 1,204 bp · p 0.27 · regional, not allelic
Overall
CADD	17.97	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

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: BCL3
Protein: p.Pro418Ala
Coding: c.1252C>G
MANE Select: NM_005178
dbSNP: rs1967380597
Type: single nucleotide variant
Location: chr19:44759502 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 71.86 · 2 PDB
Residue 418: the 'disordered' region

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-pro418ala (accessed [today's date]).

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