Is BACH2 p.Thr83= (c.249A>G) pathogenic?

BACH2 p.Thr83= (c.249A>G) is classified Benign in BACH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 67.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 60.

What condition is associated with BACH2 p.Thr83= (c.249A>G)?

BACH2 p.Thr83= (c.249A>G) is associated with immunodeficiency 60 (ClinVar).

BACH2 p.Thr83=

Q: How common is BACH2 p.Thr83= (c.249A>G) in the general population?

BACH2 p.Thr83= (c.249A>G) is common (popmax 67.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.249A>G · rs2236181 · VCV1166323

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 67.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency 60

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.8	GERP -3.7
Overall
CADD	2.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 67.7% East Asian · 30,298/44,740 alleles

Filtering AF 67.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.8%

Overall 38.7% 623,207/1,608,632 alleles · common exomes 561,308/1,456,512 · genomes 61,899/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	67.7%	1
African / African-American	44.9%	2
South Asian	43.9%	2
Amishnot grpmax-eligible	41.9%	2
Admixed American	41.8%	2
Finnishnot grpmax-eligible	40.4%	2
Remaining individualsnot grpmax-eligible	39.4%	3
European (non-Finnish)	36.7%	3
Ashkenazi Jewishnot grpmax-eligible	35.6%	3
Middle Eastern	31.9%	3

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.Thr83=
Coding: c.249A>G
MANE Select: NM_021813
dbSNP: rs2236181
Type: single nucleotide variant
Location: chr6:89951857 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 83: the btb domain

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.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
BACH2 p.Pro368Ser 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-thr83 (accessed [today's date]).

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