Is BACH2 p.Arg151Pro (c.452G>C) pathogenic?

BACH2 p.Arg151Pro (c.452G>C) is classified Likely benign in BACH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1118); Rare (popmax 0.536%, afr).

How common is BACH2 p.Arg151Pro (c.452G>C) in the general population?

BACH2 p.Arg151Pro (c.452G>C) is rare (popmax 0.536%, afr) (gnomAD).

What do computational predictors say about BACH2 p.Arg151Pro (c.452G>C)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

BACH2 p.Arg151Pro

c.452G>C · rs144637668 · VCV1556140

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.536%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -5.39	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 3.3	GERP -0.14, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 279 bp · p 0.18 · regional, not allelic
Overall
CADD	16.74	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 0.536% African / African-American · 402/75,060 alleles

Filtering AF 0.492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.475%

Overall 0.0277% 447/1,614,212 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.536%	187
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.0283%	3,531
South Asian	0.0022%	45,544
European (non-Finnish)	8.47e-05%	1,180,032

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.Arg151Pro
Coding: c.452G>C
MANE Select: NM_021813
dbSNP: rs144637668
Type: single nucleotide variant
Location: chr6:89951654 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB

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

Similar variants

BACH2 p.Arg151His Uncertain significance ★ ⚠ 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-arg151pro (accessed [today's date]).

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