Is BACH2 p.Leu24Pro (c.71T>C) pathogenic?

BACH2 p.Leu24Pro (c.71T>C) is classified Pathogenic in BACH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with immunodeficiency 60.

What condition is associated with BACH2 p.Leu24Pro (c.71T>C)?

BACH2 p.Leu24Pro (c.71T>C) is associated with immunodeficiency 60 (ClinVar).

How common is BACH2 p.Leu24Pro (c.71T>C) in the general population?

BACH2 p.Leu24Pro (c.71T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACH2 p.Leu24Pro (c.71T>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

BACH2 p.Leu24Pro

c.71T>C · rs1562364898 · VCV625843

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 60

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 1% in BACH2
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -14.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 57 kb · p 5.7e-11 · regional, not allelic
Overall
CADD	31.0	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

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: BACH2
Protein: p.Leu24Pro
Coding: c.71T>C
MANE Select: NM_021813
dbSNP: rs1562364898
Type: single nucleotide variant
Location: chr6:90008774 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 24: a UniProt-annotated variant site (in imd60; impairs protein stability; the mutant is unsoluble and forms multiple aggregates); an α-helix

Full BACH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 60 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BACH2 p.Leu24= Likely benign ★ same residue
BACH2 p.Ala148Val Uncertain significance ★★ ⚠ same condition
BACH2 p.Ala756Val Uncertain significance ★★ ⚠ same condition
BACH2 p.Asp34Asn Uncertain significance ★★ ⚠ same condition
BACH2 p.Gln378His Uncertain significance ★★ ⚠ same condition
BACH2 p.Gln578Lys Uncertain significance ★★ ⚠ same condition
BACH2 p.Glu788Lys Uncertain significance ★★ ⚠ same condition
BACH2 p.Pro152Leu Uncertain significance ★★ ⚠ same condition

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/bach2-p-leu24pro (accessed [today's date]).

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