Is BACH2 p.Thr319Ala (c.955A>G) pathogenic?

BACH2 p.Thr319Ala (c.955A>G) is classified Conflicting classifications of pathogenicity in BACH2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-06-24). AlphaMissense: likely benign (0.0556); Ultra-rare (popmax 0.0233%, sas); Associated with immunodeficiency 60.

What condition is associated with BACH2 p.Thr319Ala (c.955A>G)?

BACH2 p.Thr319Ala (c.955A>G) is associated with immunodeficiency 60 (ClinVar).

How common is BACH2 p.Thr319Ala (c.955A>G) in the general population?

BACH2 p.Thr319Ala (c.955A>G) is ultra-rare (popmax 0.0233%, sas) (gnomAD).

What do computational predictors say about BACH2 p.Thr319Ala (c.955A>G)?

AlphaMissense predicts likely benign (score 0.0556) — an in-silico prediction, not a clinical call.

BACH2 p.Thr319Ala

c.955A>G · rs754815178 · VCV636831

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0556 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 60

Computational evidence

Protein change
AlphaMissense	0.0556	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.58	GERP -3.1
Regional constraint	o/e 0.99	unconstrained · MANE · 534 bp · p 0.87 · regional, not allelic
Overall
CADD	0.032	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 0.0233% South Asian · 20/85,816 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00195% 31/1,590,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0233%	4,291
Middle Eastern	0.0212%	4,710
European (non-Finnish)	0.000855%	116,960

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.Thr319Ala
Coding: c.955A>G
MANE Select: NM_021813
dbSNP: rs754815178
Type: single nucleotide variant
Location: chr6:89951151 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 319: the 'disordered' region

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-thr319ala (accessed [today's date]).

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