Is BCL6 p.Phe213Leu (c.637T>C) pathogenic?

BCL6 p.Phe213Leu (c.637T>C) is classified Likely benign in BCL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely pathogenic (0.7521); Absent from gnomAD v4.1.

How common is BCL6 p.Phe213Leu (c.637T>C) in the general population?

BCL6 p.Phe213Leu (c.637T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL6 p.Phe213Leu (c.637T>C)?

AlphaMissense predicts likely pathogenic (score 0.7521) — an in-silico prediction, not a clinical call.

BCL6 p.Phe213Leu

c.637T>C · VCV3991025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7521 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7521	likely pathogenic
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.04	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 592 bp · p 0.79 · regional, not allelic
Overall
CADD	14.31	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

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: BCL6
Protein: p.Phe213Leu
Coding: c.637T>C
MANE Select: NM_001706
Type: single nucleotide variant
Location: chr3:187729768 (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 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-phe213leu (accessed [today's date]).

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