Is BMP6 p.Ala189= (c.567C>T) pathogenic?

BMP6 p.Ala189= (c.567C>T) is classified Likely benign in BMP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-20). Ultra-rare (popmax 0.047%, eas); Associated with BMP6-related disorder.

What condition is associated with BMP6 p.Ala189= (c.567C>T)?

BMP6 p.Ala189= (c.567C>T) is associated with BMP6-related disorder (ClinVar).

How common is BMP6 p.Ala189= (c.567C>T) in the general population?

BMP6 p.Ala189= (c.567C>T) is ultra-rare (popmax 0.047%, eas) (gnomAD).

BMP6 p.Ala189=

c.567C>T · rs533077681 · VCV3053296

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.047%, eas)

Conditions

BMP6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3.5
Overall
CADD	6.072	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.047% East Asian · 21/44,648 alleles

Filtering AF 0.0315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0264%

Overall 0.0015% 24/1,596,094 alleles · ultra-rare exomes 21/1,443,762 · genomes 3/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.047%	2,126
Remaining individualsnot grpmax-eligible	0.00161%	62,118
European (non-Finnish)	0.00017%	588,890

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: BMP6
Protein: p.Ala189=
Coding: c.567C>T
MANE Select: NM_001718
dbSNP: rs533077681
Type: single nucleotide variant
Location: chr6:7727522 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 69.74 · 5 PDB
Residue 189: a UniProt-annotated variant site (in io; associated with disease susceptibility); the 'disordered' region

Full BMP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BMP6-related disorder

Similar variants

BMP6 p.Ala189Thr Benign same residue
BMP6 c.1392+7T>G Likely benign same condition
BMP6 c.665-3T>C Likely benign same condition
BMP6 p.Ala212= Benign same condition
BMP6 p.Ala343= Benign same condition
BMP6 p.Arg28Gln Benign same condition
BMP6 p.Arg396= Likely benign same condition
BMP6 p.Asp354= Benign same condition

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/bmp6-p-ala189 (accessed [today's date]).

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