Is BACH2 p.Leu291Val (c.871C>G) pathogenic?

BACH2 p.Leu291Val (c.871C>G) is classified Benign in BACH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1296); Low-frequency (popmax 3.18%, nfe).

How common is BACH2 p.Leu291Val (c.871C>G) in the general population?

BACH2 p.Leu291Val (c.871C>G) is low-frequency (popmax 3.18%, nfe) (gnomAD).

What do computational predictors say about BACH2 p.Leu291Val (c.871C>G)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

BACH2 p.Leu291Val

c.871C>G · rs61754114 · VCV1167842

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.18%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -5.26	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 8.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 534 bp · p 0.87 · regional, not allelic
Overall
CADD	24.1	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 3.18% European (non-Finnish) · 37,522/1,180,014 alleles

Filtering AF 3.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.14%

Overall 2.76% 44,493/1,614,114 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.59%	28
European (non-Finnish)grpmax	3.18%	31
Remaining individualsnot grpmax-eligible	3.17%	32
South Asian	2.62%	38
Middle Eastern	2.38%	42
Admixed American	0.935%	107
Finnishnot grpmax-eligible	0.689%	145
African / African-American	0.501%	200
Amishnot grpmax-eligible	0.219%	456
East Asian	0.0201%	4,984

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu291Val
Coding: c.871C>G
MANE Select: NM_021813
dbSNP: rs61754114
Type: single nucleotide variant
Location: chr6:89951235 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 291: the 'disordered' region

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

Similar variants

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
BACH2 p.Ala761Ser 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-leu291val (accessed [today's date]).

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