Is BACH2 p.Pro801Leu (c.2402C>T) pathogenic?

BACH2 p.Pro801Leu (c.2402C>T) is classified Uncertain significance in BACH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0722); Ultra-rare (popmax 0.0346%, nfe).

How common is BACH2 p.Pro801Leu (c.2402C>T) in the general population?

BACH2 p.Pro801Leu (c.2402C>T) is ultra-rare (popmax 0.0346%, nfe) (gnomAD).

What do computational predictors say about BACH2 p.Pro801Leu (c.2402C>T)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

BACH2 p.Pro801Leu

c.2402C>T · rs201359587 · VCV1408084

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.42	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 6.1	GERP 0.59, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 320 bp · p 0.52 · regional, not allelic
Overall
CADD	21.7	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 0.0346% European (non-Finnish) · 408/1,180,014 alleles

Filtering AF 0.0318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0307%

Overall 0.0293% 473/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0346%	2,892
South Asian	0.0275%	3,643
Admixed American	0.0233%	4,286
Remaining individualsnot grpmax-eligible	0.0208%	4,808
African / African-American	0.012%	8,332
East Asian	0.00891%	11,220

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.Pro801Leu
Coding: c.2402C>T
MANE Select: NM_021813
dbSNP: rs201359587
Type: single nucleotide variant
Location: chr6:89932532 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 801: the 'disordered' region

Full BACH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BACH2 p.Pro801= Likely benign ★ same residue
BACH2 p.Ala148Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala205Thr Uncertain significance ★★ ⚠ same type
BACH2 p.Ala304Glu Uncertain significance ★★ ⚠ same type
BACH2 p.Ala479Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala529Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala747Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala756Val 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/bach2-p-pro801leu (accessed [today's date]).

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