Is BCL6 p.Ser434Arg (c.1302C>A) pathogenic?

BCL6 p.Ser434Arg (c.1302C>A) is classified Uncertain significance in BCL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: ambiguous (0.3511); Very rare (popmax 7.12e-05%).

How common is BCL6 p.Ser434Arg (c.1302C>A) in the general population?

BCL6 p.Ser434Arg (c.1302C>A) is very rare (popmax 7.12e-05%) (gnomAD).

What do computational predictors say about BCL6 p.Ser434Arg (c.1302C>A)?

AlphaMissense predicts ambiguous (score 0.3511) — an in-silico prediction, not a clinical call.

BCL6 p.Ser434Arg

c.1302C>A · rs765760636 · VCV3133434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3511 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.12e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3511	ambiguous
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.36	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -4.1
Regional constraint	o/e 0.97	unconstrained · MANE · 2,447 bp · p 0.65 · regional, not allelic
Overall
CADD	0.142	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 7.12e-05%

Overall 7.12e-05% 1/1,404,364 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: BCL6
Protein: p.Ser434Arg
Coding: c.1302C>A
MANE Select: NM_001706
dbSNP: rs765760636
Type: single nucleotide variant
Location: chr3:187729103 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.89 · 222 PDB
Residue 434: the 'disordered' region

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

Similar variants

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.Pro245= 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-ser434arg (accessed [today's date]).

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