Is BCL6B p.Ser65Pro (c.193T>C) pathogenic?

BCL6B p.Ser65Pro (c.193T>C) is classified Uncertain significance in BCL6B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). AlphaMissense: likely pathogenic (0.9127); Very rare (popmax 8.47e-05%, nfe).

How common is BCL6B p.Ser65Pro (c.193T>C) in the general population?

BCL6B p.Ser65Pro (c.193T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BCL6B p.Ser65Pro (c.193T>C)?

AlphaMissense predicts likely pathogenic (score 0.9127) — an in-silico prediction, not a clinical call.

BCL6B p.Ser65Pro

c.193T>C · VCV3260663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9127 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9127	likely pathogenic
REVEL	0.513	indeterminate
SaProt	LLR -9.55	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 6.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,944 bp · p 0.3 · regional, not allelic
Overall
CADD	28.2	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 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.84e-05% 1/1,461,672 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: BCL6B
Protein: p.Ser65Pro
Coding: c.193T>C
MANE Select: NM_181844
Type: single nucleotide variant
Location: chr17:7024096 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.79
Residue 65: the btb domain

Full BCL6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL6B p.Ala209Pro Uncertain significance ★ ⚠ same type
BCL6B p.Arg143His Uncertain significance ★ ⚠ same type
BCL6B p.Arg163Cys Uncertain significance ★ ⚠ same type
BCL6B p.Arg19Gly Uncertain significance ★ same type
BCL6B p.Arg34Cys Uncertain significance ★ ⚠ same type
BCL6B p.Asp231Glu Uncertain significance ★ ⚠ same type
BCL6B p.Gln179Arg Uncertain significance ★ ⚠ same type
BCL6B p.Glu8Asp 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/bcl6b-p-ser65pro (accessed [today's date]).

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