Is BACH1 p.Asp294Val (c.881A>T) pathogenic?

BACH1 p.Asp294Val (c.881A>T) is classified Uncertain significance in BACH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0779); Ultra-rare (popmax 0.0312%, eas).

How common is BACH1 p.Asp294Val (c.881A>T) in the general population?

BACH1 p.Asp294Val (c.881A>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about BACH1 p.Asp294Val (c.881A>T)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

BACH1 p.Asp294Val

c.881A>T · rs762633394 · VCV3132789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.68	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 1.9	GERP 1.9, phastCons 0.81
Regional constraint	o/e 0.93	unconstrained · MANE · 22 kb · p 0.029 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0312% East Asian · 14/44,904 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000867% 14/1,614,058 alleles · ultra-rare exomes 11/1,461,836 · genomes 3/152,222 · joint denominator

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: BACH1
Protein: p.Asp294Val
Coding: c.881A>T
MANE Select: NM_001186
dbSNP: rs762633394
Type: single nucleotide variant
Location: chr21:29326705 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.17 · 12 PDB
Residue 294: the 'disordered' region

Full BACH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BACH1 p.Ala193Gly Uncertain significance ★ ⚠ same type
BACH1 p.Ala203Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala233Gly Uncertain significance ★ ⚠ same type
BACH1 p.Ala285Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala382Glu Uncertain significance ★ ⚠ same type
BACH1 p.Ala382Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala665Val Uncertain significance ★ ⚠ same type
BACH1 p.Ala678Thr 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/bach1-p-asp294val (accessed [today's date]).

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