Is BACH2 p.Arg666Lys (c.1997G>A) pathogenic?

BACH2 p.Arg666Lys (c.1997G>A) is classified Uncertain significance in BACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-28). AlphaMissense: likely pathogenic (0.9923); Absent from gnomAD v4.1.

How common is BACH2 p.Arg666Lys (c.1997G>A) in the general population?

BACH2 p.Arg666Lys (c.1997G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACH2 p.Arg666Lys (c.1997G>A)?

AlphaMissense predicts likely pathogenic (score 0.9923) — an in-silico prediction, not a clinical call.

BACH2 p.Arg666Lys

c.1997G>A · rs2533545914 · VCV1999840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9923	likely pathogenic · top 7% in BACH2
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -10.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 18 kb · p 2.2e-13 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Arg666Lys
Coding: c.1997G>A
MANE Select: NM_021813
dbSNP: rs2533545914
Type: single nucleotide variant
Location: chr6:89938190 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 666: the bzip domain; the 'basic motif' 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-arg666lys (accessed [today's date]).

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