Is BACH2 p.Leu133= (c.399C>G) pathogenic?

BACH2 p.Leu133= (c.399C>G) is classified Likely benign in BACH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-06). Ultra-rare (popmax 0.078%, eas).

How common is BACH2 p.Leu133= (c.399C>G) in the general population?

BACH2 p.Leu133= (c.399C>G) is ultra-rare (popmax 0.078%, eas) (gnomAD).

BACH2 p.Leu133=

c.399C>G · rs570273534 · VCV1674916

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.7, phastCons 1
Overall
CADD	13.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.078% East Asian · 35/44,882 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.00452% 73/1,614,242 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.078%	1,282
South Asian	0.0263%	3,795
Remaining individualsnot grpmax-eligible	0.0144%	6,946
European (non-Finnish)	0.000424%	236,010

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: BACH2
Protein: p.Leu133=
Coding: c.399C>G
MANE Select: NM_021813
dbSNP: rs570273534
Type: single nucleotide variant
Location: chr6:89951707 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB

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

Similar variants

BACH2 p.Ala148Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala205Thr Uncertain significance ★★ ⚠ same type
BACH2 p.Ala304Glu Uncertain significance ★★ ⚠ same type
BACH2 p.Ala479Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala529Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala747Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala756Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala761Ser 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/bach2-p-leu133 (accessed [today's date]).

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