Is BACH1 p.Arg44Trp (c.130C>T) pathogenic?

BACH1 p.Arg44Trp (c.130C>T) is classified Uncertain significance in BACH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: likely benign (0.1787); Ultra-rare (popmax 0.0164%, mid).

How common is BACH1 p.Arg44Trp (c.130C>T) in the general population?

BACH1 p.Arg44Trp (c.130C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BACH1 p.Arg44Trp (c.130C>T)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

BACH1 p.Arg44Trp

c.130C>T · VCV3474304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.18, phastCons 0.78
Overall
CADD	24.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00097%

Overall 0.00155% 25/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00178%	56,193
Admixed American	0.00167%	60,004
Finnishnot grpmax-eligible	0.00156%	64,038
African / African-American	0.00133%	74,916

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: BACH1
Protein: p.Arg44Trp
Coding: c.130C>T
MANE Select: NM_032043 · reported on NM_001186
Type: single nucleotide variant
Location: chr21:29321410 (GRCh38)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 44: the helicase atp-binding domain

Full BACH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRIP1 p.Leu44= Benign/Likely benign ★★ same residue
BACH1 p.Arg44Gln Uncertain significance ★ ⚠ same residue
BRIP1 p.Leu44Trp Uncertain significance ★ ⚠ same residue
BRIP1 p.Leu44fs Pathogenic ★ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same type
BRIP1 c.1141-2A>C Likely pathogenic ★★ same type
BRIP1 c.1141-2A>G Likely pathogenic ★★ same type
BRIP1 c.1141-2A>T Likely pathogenic ★★ 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/bach1-p-arg44trp (accessed [today's date]).

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