Is BACH2 p.Glu645Asp (c.1935G>T) pathogenic?

BACH2 p.Glu645Asp (c.1935G>T) is classified Uncertain significance in BACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-13). AlphaMissense: ambiguous (0.4881); Ultra-rare (popmax 0.0357%, eas).

How common is BACH2 p.Glu645Asp (c.1935G>T) in the general population?

BACH2 p.Glu645Asp (c.1935G>T) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about BACH2 p.Glu645Asp (c.1935G>T)?

AlphaMissense predicts ambiguous (score 0.4881) — an in-silico prediction, not a clinical call.

BACH2 p.Glu645Asp

c.1935G>T · rs201170817 · VCV2195021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4881	ambiguous
REVEL	0.286	benign-leaning
SaProt	LLR -5.89	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.53, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 18 kb · p 2.2e-13 · regional, not allelic
Overall
CADD	20.5	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 0.0357% East Asian · 16/44,878 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.000991% 16/1,614,268 alleles · ultra-rare

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.Glu645Asp
Coding: c.1935G>T
MANE Select: NM_021813
dbSNP: rs201170817
Type: single nucleotide variant
Location: chr6:89938252 (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.Glu645= 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-glu645asp (accessed [today's date]).

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