Is BMP6 p.Glu75= (c.225G>A) pathogenic?

BMP6 p.Glu75= (c.225G>A) is classified Benign in BMP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Rare (popmax 0.383%, nfe); Associated with BMP6-related disorder.

What condition is associated with BMP6 p.Glu75= (c.225G>A)?

BMP6 p.Glu75= (c.225G>A) is associated with BMP6-related disorder (ClinVar).

How common is BMP6 p.Glu75= (c.225G>A) in the general population?

BMP6 p.Glu75= (c.225G>A) is rare (popmax 0.383%, nfe) (gnomAD).

BMP6 p.Glu75=

c.225G>A · rs201788022 · VCV3056390

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.383%, nfe)

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 5.2	GERP 0.6, phastCons 1
Overall
CADD	13.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.383% European (non-Finnish) · 4,497/1,174,088 alleles

Filtering AF 0.374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.37%

Overall 0.373% 5,972/1,599,744 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.21%	83
Finnishnot grpmax-eligible	1.18%	85
Remaining individualsnot grpmax-eligible	0.405%	247
European (non-Finnish)grpmax	0.383%	261
Admixed American	0.145%	689
African / African-American	0.0738%	1,355
South Asian	0.0178%	5,609
Middle Eastern	0.0167%	5,984

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu75=
Coding: c.225G>A
MANE Select: NM_001718
dbSNP: rs201788022
Type: single nucleotide variant
Location: chr6:7727180 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 69.74 · 5 PDB

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

Disease context

BMP6-related disorder

Similar variants

BMP6 c.1392+7T>G Likely benign same condition
BMP6 c.665-3T>C Likely benign same condition
BMP6 p.Ala189= Likely benign same condition
BMP6 p.Ala189Thr 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

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-glu75 (accessed [today's date]).

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