Is BMP7 p.Pro116= (c.348C>G) pathogenic?

BMP7 p.Pro116= (c.348C>G) is classified Likely benign in BMP7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-02). Ultra-rare (popmax 0.0227%, afr); Associated with BMP7-related disorder.

What condition is associated with BMP7 p.Pro116= (c.348C>G)?

BMP7 p.Pro116= (c.348C>G) is associated with BMP7-related disorder (ClinVar).

How common is BMP7 p.Pro116= (c.348C>G) in the general population?

BMP7 p.Pro116= (c.348C>G) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

BMP7 p.Pro116=

c.348C>G · VCV3355061

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

BMP7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.595	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.9, phastCons 1
Overall
CADD	12.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,890 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00118% 19/1,610,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,405
Remaining individualsnot grpmax-eligible	0.00321%	31,153

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.Pro116=
Coding: c.348C>G
MANE Select: NM_001719
Type: single nucleotide variant
Location: chr20:57265775 (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

BMP7-related disorder

Similar variants

BMP7 p.Pro116Ser Uncertain significance ★★ ⚠ same residue
BMP7 p.Leu160Phe Uncertain significance ★★ ⚠ same condition
BMP7 p.Ser248Leu Uncertain significance ★★ ⚠ same condition
BMP7 p.Ala329Gly Uncertain significance ★ ⚠ same condition
BMP7 p.Val415Ile Uncertain significance ★ ⚠ same condition
BMP7 p.Ala29Ser Uncertain significance ⚠ same condition
BMP7 p.Asn368= Likely benign same condition
BMP7 p.Gln49= 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/bmp7-p-pro116 (accessed [today's date]).

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