Is BACH2 p.Tyr385Cys (c.1154A>G) pathogenic?

BACH2 p.Tyr385Cys (c.1154A>G) is classified Conflicting classifications of pathogenicity in BACH2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1139); Rare (popmax 0.125%, sas).

How common is BACH2 p.Tyr385Cys (c.1154A>G) in the general population?

BACH2 p.Tyr385Cys (c.1154A>G) is rare (popmax 0.125%, sas) (gnomAD).

What do computational predictors say about BACH2 p.Tyr385Cys (c.1154A>G)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

BACH2 p.Tyr385Cys

c.1154A>G · rs770481670 · VCV2152494

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -5.51	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 4.3	GERP 0.41, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 534 bp · p 0.87 · regional, not allelic
Overall
CADD	24.0	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 0.125% South Asian · 104/83,154 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0983%

Overall 0.00687% 108/1,571,700 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.125%	800
Remaining individualsnot grpmax-eligible	0.00495%	20,184
European (non-Finnish)	8.63e-05%	1,159,268

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.Tyr385Cys
Coding: c.1154A>G
MANE Select: NM_021813
dbSNP: rs770481670
Type: single nucleotide variant
Location: chr6:89950952 (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.Tyr385Asp Uncertain significance ★ ⚠ same residue
BACH2 p.Tyr385= 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

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-tyr385cys (accessed [today's date]).

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