Is BACH2 p.Cys500Phe (c.1499G>T) pathogenic?

BACH2 p.Cys500Phe (c.1499G>T) is classified Uncertain significance in BACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely pathogenic (0.9107); Very rare (popmax 0.000657%).

How common is BACH2 p.Cys500Phe (c.1499G>T) in the general population?

BACH2 p.Cys500Phe (c.1499G>T) is very rare (popmax 0.000657%) (gnomAD).

What do computational predictors say about BACH2 p.Cys500Phe (c.1499G>T)?

AlphaMissense predicts likely pathogenic (score 0.9107) — an in-silico prediction, not a clinical call.

BACH2 p.Cys500Phe

c.1499G>T · rs1203834121 · VCV2810063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000657%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9107	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -5.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 220 bp · p 0.69 · regional, not allelic
Overall
CADD	27.2	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 0.000657%

Overall 0.000657% 1/152,188 alleles · very 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.Cys500Phe
Coding: c.1499G>T
MANE Select: NM_021813
dbSNP: rs1203834121
Type: single nucleotide variant
Location: chr6:89950607 (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-cys500phe (accessed [today's date]).

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