Is BCL6 p.Pro245Leu (c.734C>T) pathogenic?

BCL6 p.Pro245Leu (c.734C>T) is classified Uncertain significance in BCL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1222); Ultra-rare (popmax 0.0395%, sas).

How common is BCL6 p.Pro245Leu (c.734C>T) in the general population?

BCL6 p.Pro245Leu (c.734C>T) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

What do computational predictors say about BCL6 p.Pro245Leu (c.734C>T)?

AlphaMissense predicts likely benign (score 0.1222) — an in-silico prediction, not a clinical call.

BCL6 p.Pro245Leu

c.734C>T · rs560916500 · VCV2375099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1222 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1222	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.19	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 5.2	GERP -0.96, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 592 bp · p 0.79 · regional, not allelic
Overall
CADD	18.01	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 0.0395% South Asian · 36/91,082 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00551% 89/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,530
African / African-American	0.00533%	18,759
European (non-Finnish)	0.00407%	24,584
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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: BCL6
Protein: p.Pro245Leu
Coding: c.734C>T
MANE Select: NM_001706
dbSNP: rs560916500
Type: single nucleotide variant
Location: chr3:187729671 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.89 · 222 PDB

Full BCL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL6 p.Pro245= Likely benign ★★ same residue
BCL6 c.1356-3T>C Likely benign ★★ same type
BCL6 c.161+8A>T Benign ★★ same type
BCL6 c.1840-7C>T Likely benign ★★ same type
BCL6 p.Ser209= Benign ★★ same type
BCL6 p.Thr48= Benign ★★ same type
BCL6 p.Ala107Thr Uncertain significance ★ ⚠ same type
BCL6 p.Ala291Thr 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/bcl6-p-pro245leu (accessed [today's date]).

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