Is BACH1 p.Ser537Pro (c.1609T>C) pathogenic?

BACH1 p.Ser537Pro (c.1609T>C) is classified Uncertain significance in BACH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely pathogenic (0.8296); Very rare (popmax 8.51e-05%, nfe).

How common is BACH1 p.Ser537Pro (c.1609T>C) in the general population?

BACH1 p.Ser537Pro (c.1609T>C) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about BACH1 p.Ser537Pro (c.1609T>C)?

AlphaMissense predicts likely pathogenic (score 0.8296) — an in-silico prediction, not a clinical call.

BACH1 p.Ser537Pro

c.1609T>C · rs2516624525 · VCV3132783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8296	likely pathogenic
REVEL	0.386	indeterminate
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.69, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 22 kb · p 0.029 · regional, not allelic
Overall
CADD	23.9	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 8.51e-05% European (non-Finnish) · 1/1,174,628 alleles

Overall 6.25e-05% 1/1,600,002 alleles · very rare exomes 1/1,447,668 · genomes 0/152,334 · joint denominator

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.Ser537Pro
Coding: c.1609T>C
MANE Select: NM_001186
dbSNP: rs2516624525
Type: single nucleotide variant
Location: chr21:29329526 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.17 · 12 PDB

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

Similar variants

BACH1 p.Ala193Gly Uncertain significance ★ ⚠ same type
BACH1 p.Ala203Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala233Gly Uncertain significance ★ ⚠ same type
BACH1 p.Ala285Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala382Glu Uncertain significance ★ ⚠ same type
BACH1 p.Ala382Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala665Val Uncertain significance ★ ⚠ same type
BACH1 p.Ala678Thr 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/bach1-p-ser537pro (accessed [today's date]).

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