Is BACH2 p.Pro357= (c.1071C>T) pathogenic?

BACH2 p.Pro357= (c.1071C>T) is classified Benign in BACH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 28.4%, eas) — too common for a highly-penetrant pathogenic allele.

BACH2 p.Pro357=

Q: How common is BACH2 p.Pro357= (c.1071C>T) in the general population?

BACH2 p.Pro357= (c.1071C>T) is common (popmax 28.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1071C>T · rs2236182 · VCV1166322

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 28.4%, eas) — too common for a highly-penetrant pathogenic allele

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 1.6	GERP -1.5, phastCons 0.91
Overall
CADD	6.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.4% East Asian · 12,703/44,784 alleles

Filtering AF 28% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.8%

Overall 1.95% 31,340/1,607,872 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	28.4%	4
Admixed American	12.9%	8
Finnishnot grpmax-eligible	5.22%	19
Remaining individualsnot grpmax-eligible	2.25%	44
Ashkenazi Jewishnot grpmax-eligible	1.33%	75
South Asian	0.902%	111
African / African-American	0.434%	230
European (non-Finnish)	0.404%	247
Middle Eastern	0.266%	376

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.Pro357=
Coding: c.1071C>T
MANE Select: NM_021813
dbSNP: rs2236182
Type: single nucleotide variant
Location: chr6:89951035 (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-pro357 (accessed [today's date]).

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