Is BACH2 p.Leu615Ile (c.1843C>A) pathogenic?

BACH2 p.Leu615Ile (c.1843C>A) is classified Uncertain significance in BACH2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6859); Absent from gnomAD v4.1.

How common is BACH2 p.Leu615Ile (c.1843C>A) in the general population?

BACH2 p.Leu615Ile (c.1843C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACH2 p.Leu615Ile (c.1843C>A)?

AlphaMissense predicts likely pathogenic (score 0.6859) — an in-silico prediction, not a clinical call.

BACH2 p.Leu615Ile

c.1843C>A · rs2128353846 · VCV1049033

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6859 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6859	likely pathogenic
REVEL	0.16	moderately benign-leaning
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 18 kb · p 2.2e-13 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BACH2
Protein: p.Leu615Ile
Coding: c.1843C>A
MANE Select: NM_021813
dbSNP: rs2128353846
Type: single nucleotide variant
Location: chr6:89938344 (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.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-leu615ile (accessed [today's date]).

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