Is BACH1 p.Leu212Phe (c.636A>T) pathogenic?

BACH1 p.Leu212Phe (c.636A>T) is classified Uncertain significance in BACH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.0078%, nfe).

How common is BACH1 p.Leu212Phe (c.636A>T) in the general population?

BACH1 p.Leu212Phe (c.636A>T) is very rare (popmax 0.0078%, nfe) (gnomAD).

What do computational predictors say about BACH1 p.Leu212Phe (c.636A>T)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

BACH1 p.Leu212Phe

c.636A>T · VCV3984289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0078%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -7.81	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 0.9	GERP -3.5, phastCons 0.083
Overall
CADD	11.38	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0078% European (non-Finnish) · 92/1,180,046 alleles

Filtering AF 0.00647% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.00589% 95/1,614,120 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0078%	12,827
Remaining individualsnot grpmax-eligible	0.0032%	31,245
Finnishnot grpmax-eligible	0.00156%	64,046

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.Leu212Phe
Coding: c.636A>T
MANE Select: NM_032043 · reported on NM_001186
Type: single nucleotide variant
Location: chr21:29326460 (GRCh38)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 212: the helicase atp-binding domain

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

Similar variants

BRIP1 p.Gly212Arg Uncertain significance ★★ ⚠ same residue
BRIP1 p.Gly212Ser Uncertain significance ★★ ⚠ same residue
BRIP1 p.Gly212= Benign/Likely benign ★★ same residue
BRIP1 p.Gly212Asp Uncertain significance ★ ⚠ same residue
BRIP1 p.Gly212fs 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

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-leu212phe (accessed [today's date]).

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