Is BCL7B p.Ser2Leu (c.5C>T) pathogenic?

BCL7B p.Ser2Leu (c.5C>T) is classified Uncertain significance in BCL7B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.966); Very rare (popmax 0.00199%, sas).

How common is BCL7B p.Ser2Leu (c.5C>T) in the general population?

BCL7B p.Ser2Leu (c.5C>T) is very rare (popmax 0.00199%, sas) (gnomAD).

What do computational predictors say about BCL7B p.Ser2Leu (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.966) — an in-silico prediction, not a clinical call.

BCL7B p.Ser2Leu

c.5C>T · VCV4645491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00199%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.966	likely pathogenic
REVEL	0.233	benign-leaning
SaProt	LLR -12.11	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 20 kb · p 0.0024 · regional, not allelic
Overall
CADD	33.0	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 0.00199% South Asian · 1/50,374 alleles

Overall 0.000169% 2/1,181,990 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00199%	50,374
European (non-Finnish)	9.71e-05%	1,029,682

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: BCL7B
Protein: p.Ser2Leu
Coding: c.5C>T
MANE Select: NM_001707
Type: single nucleotide variant
Location: chr7:73557574 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 3 PDB

Full BCL7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL7B p.Ala155Gly Uncertain significance ★ ⚠ same type
BCL7B p.Arg130Cys Uncertain significance ★ ⚠ same type
BCL7B p.Arg187Pro Uncertain significance ★ ⚠ same type
BCL7B p.His125Leu Uncertain significance ★ ⚠ same type
BCL7B p.His125Pro Uncertain significance ★ ⚠ same type
BCL7B p.Leu83Pro Uncertain significance ★ ⚠ same type
BCL7B p.Phe73Leu Uncertain significance ★ ⚠ same type
BCL7B p.Pro115Leu 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/bcl7b-p-ser2leu (accessed [today's date]).

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