Is BACH1 p.Arg28Trp (c.82C>T) pathogenic?

BACH1 p.Arg28Trp (c.82C>T) is classified Uncertain significance in BACH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.8183); Very rare (popmax 0.00186%, nfe).

How common is BACH1 p.Arg28Trp (c.82C>T) in the general population?

BACH1 p.Arg28Trp (c.82C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about BACH1 p.Arg28Trp (c.82C>T)?

AlphaMissense predicts likely pathogenic (score 0.8183) — an in-silico prediction, not a clinical call.

BACH1 p.Arg28Trp

c.82C>T · rs747087328 · VCV2468482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8183 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8183	likely pathogenic
REVEL	0.698	pathogenic-leaning
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.73, phastCons 1
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 0.00186% European (non-Finnish) · 22/1,180,038 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,614,066 alleles · very rare

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.Arg28Trp
Coding: c.82C>T
MANE Select: NM_032043 · reported on NM_001186
dbSNP: rs747087328
Type: single nucleotide variant
Location: chr21:29321362 (GRCh38)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 28: the helicase atp-binding domain

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

Similar variants

BRIP1 p.Met28Leu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Met28Lys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Met28Val Uncertain significance ★★ ⚠ 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
BRIP1 c.1340+1G>A Pathogenic/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-arg28trp (accessed [today's date]).

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