Is BMP7 p.Arg289His (c.866G>A) pathogenic?

BMP7 p.Arg289His (c.866G>A) is classified Uncertain significance in BMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: ambiguous (0.4907); Very rare (popmax 0.000169%, nfe); Associated with nephrotic syndrome, type 12.

What condition is associated with BMP7 p.Arg289His (c.866G>A)?

BMP7 p.Arg289His (c.866G>A) is associated with nephrotic syndrome, type 12 (ClinVar).

How common is BMP7 p.Arg289His (c.866G>A) in the general population?

BMP7 p.Arg289His (c.866G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about BMP7 p.Arg289His (c.866G>A)?

AlphaMissense predicts ambiguous (score 0.4907) — an in-silico prediction, not a clinical call.

BMP7 p.Arg289His

Q: How is Hereditary steroid-resistant nephrotic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.866G>A · rs2515997277 · VCV3064817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

nephrotic syndrome, type 12

Computational evidence

Protein change
AlphaMissense	0.4907	ambiguous
REVEL	0.609	indeterminate
SaProt	LLR -10.22	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 93 kb · p 0.00035 · regional, not allelic
Overall
CADD	26.6	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 0.000169% European (non-Finnish) · 2/1,180,044 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,854 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: BMP7
Protein: p.Arg289His
Coding: c.866G>A
MANE Select: NM_001719
dbSNP: rs2515997277
Type: single nucleotide variant
Location: chr20:57183814 (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

Disease context

nephrotic syndrome, type 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary steroid-resistant nephrotic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal

Similar variants

BMP7 p.Arg289= Likely benign ★ same residue
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

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-arg289his (accessed [today's date]).

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