Is BACH2 p.Asp620Tyr (c.1858G>T) pathogenic?

BACH2 p.Asp620Tyr (c.1858G>T) is classified Uncertain significance in BACH2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.7396); Absent from gnomAD v4.1.

How common is BACH2 p.Asp620Tyr (c.1858G>T) in the general population?

BACH2 p.Asp620Tyr (c.1858G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACH2 p.Asp620Tyr (c.1858G>T)?

AlphaMissense predicts likely pathogenic (score 0.7396) — an in-silico prediction, not a clinical call.

BACH2 p.Asp620Tyr

c.1858G>T · VCV4192052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7396 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7396	likely pathogenic
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -9.21	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.38	acceptor gain · deltas
Pangolin	Δ0.25	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP -0.53, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 18 kb · p 2.2e-13 · regional, not allelic
Overall
CADD	34.0	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

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.Asp620Tyr
Coding: c.1858G>T
MANE Select: NM_021813
Type: single nucleotide variant
Location: chr6:89938329 (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-asp620tyr (accessed [today's date]).

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