Is BMP7 p.Gln199= (c.597G>A) pathogenic?

BMP7 p.Gln199= (c.597G>A) is classified Benign in BMP7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-18). Low-frequency (popmax 3.91%, nfe).

How common is BMP7 p.Gln199= (c.597G>A) in the general population?

BMP7 p.Gln199= (c.597G>A) is low-frequency (popmax 3.91%, nfe) (gnomAD).

BMP7 p.Gln199=

c.597G>A · rs41274738 · VCV1285787

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.91%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.441	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	gain · loss 0.07 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 0.62, phastCons 1
Overall
CADD	13.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.91% European (non-Finnish) · 46,081/1,180,012 alleles

Filtering AF 3.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.86%

Overall 3.46% 55,835/1,613,682 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	8.88%	11
European (non-Finnish)grpmax	3.91%	26
Middle Eastern	3.76%	27
Ashkenazi Jewishnot grpmax-eligible	3.68%	27
Remaining individualsnot grpmax-eligible	3.48%	29
Finnishnot grpmax-eligible	3.06%	33
South Asian	2.94%	34
Admixed American	1.88%	53
African / African-American	0.569%	176
East Asian	0.0134%	7,481

Amish 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: BMP7
Protein: p.Gln199=
Coding: c.597G>A
MANE Select: NM_001719
dbSNP: rs41274738
Type: single nucleotide variant
Location: chr20:57228243 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 76.50 · 4 PDB

Full BMP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP7 p.Arg150His Uncertain significance ★★ ⚠ same type
BMP7 p.Arg267Gln Uncertain significance ★★ ⚠ same type
BMP7 p.His241Tyr Uncertain significance ★★ ⚠ same type
BMP7 p.Ile386Val Uncertain significance ★★ ⚠ same type
BMP7 p.Leu160Phe Uncertain significance ★★ same type
BMP7 p.Pro116Ser Uncertain significance ★★ ⚠ same type
BMP7 p.Ser248Leu Uncertain significance ★★ ⚠ same type
BMP7 p.Thr251Met 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/bmp7-p-gln199 (accessed [today's date]).

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