Is BMP2 p.Ile173Val (c.517A>G) pathogenic?

BMP2 p.Ile173Val (c.517A>G) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.0944); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with BMP2 p.Ile173Val (c.517A>G)?

BMP2 p.Ile173Val (c.517A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BMP2 p.Ile173Val (c.517A>G) in the general population?

BMP2 p.Ile173Val (c.517A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about BMP2 p.Ile173Val (c.517A>G)?

AlphaMissense predicts likely benign (score 0.0944) — an in-silico prediction, not a clinical call.

BMP2 p.Ile173Val

c.517A>G · rs1329513102 · VCV3134517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0944	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,670 bp · p 0.13 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,868 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: BMP2
Protein: p.Ile173Val
Coding: c.517A>G
MANE Select: NM_001200
dbSNP: rs1329513102
Type: single nucleotide variant
Location: chr20:6778415 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 173: a UniProt-annotated variant site (in ssfsc1)

Full BMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMP2 p.Arg215Gln Uncertain significance ★★ ⚠ same condition
BMP2 p.Arg291His Uncertain significance ★★ ⚠ same condition
BMP2 p.Arg6Cys Uncertain significance ★★ ⚠ same condition
BMP2 p.Glu234Gly Uncertain significance ★★ ⚠ same condition
BMP2 p.Glu235Asp Uncertain significance ★★ ⚠ same condition
BMP2 p.Gly327Arg Uncertain significance ★★ ⚠ same condition
BMP2 p.His168Asn Uncertain significance ★★ ⚠ same condition
BMP2 p.His221Arg Uncertain significance ★★ ⚠ 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/bmp2-p-ile173val (accessed [today's date]).

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