Is BMP1 p.Arg721= (c.2163A>G) pathogenic?

BMP1 p.Arg721= (c.2163A>G) is classified Likely benign in BMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). Absent from gnomAD v4.1.

How common is BMP1 p.Arg721= (c.2163A>G) in the general population?

BMP1 p.Arg721= (c.2163A>G) is absent from gnomAD v4.1 (gnomAD).

BMP1 p.Arg721=

c.2163A>G · rs2539025570 · VCV2768557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	GERP -0.97, phastCons 1
Overall
CADD	19.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMP1
Protein: p.Arg721=
Coding: c.2163A>G
MANE Select: NM_006129 · reported on NM_001199
dbSNP: rs2539025570
Type: single nucleotide variant
Location: chr8:22201173 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.89 · 8 PDB
Residue 721: a disulfide bond; the egf-like 2; calcium-binding domain

Full BMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP1 p.Arg721Ter Conflicting classifications of pathogenicity ★ same residue
BMP1 p.Arg721Gln Likely benign ★ same residue
BMP1 p.Thr721= Likely benign ★ same residue
BMP1 p.Arg721fs Uncertain significance ★ same residue
BMP1 p.Cys183Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 p.Gln70Ter Pathogenic/Likely pathogenic ★★ same type
BMP1 c.1443+6T>C Uncertain significance ★★ same type
BMP1 c.1639+4C>G 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/bmp1-p-arg721 (accessed [today's date]).

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