Is BMP2 p.His97Arg (c.290A>G) pathogenic?

BMP2 p.His97Arg (c.290A>G) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.0607); Very rare (popmax 0.00134%, afr).

How common is BMP2 p.His97Arg (c.290A>G) in the general population?

BMP2 p.His97Arg (c.290A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about BMP2 p.His97Arg (c.290A>G)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

BMP2 p.His97Arg

c.290A>G · rs1285712947 · VCV2771615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -4.88	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 4.5	GERP 0.41, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,670 bp · p 0.13 · regional, not allelic
Overall
CADD	15.46	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 0.00134% African / African-American · 1/74,854 alleles

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

Overall 0.000206% 3/1,458,554 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,854
European (non-Finnish)	0.00017%	589,199

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.His97Arg
Coding: c.290A>G
MANE Select: NM_001200
dbSNP: rs1285712947
Type: single nucleotide variant
Location: chr20:6770416 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 97: a UniProt-annotated variant site (in ssfsc1); the 'disordered' region

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

Similar variants

BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Cys329Ter Likely pathogenic ★★ same type
BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Glu229Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ser92Ter Pathogenic/Likely pathogenic ★★ same type
BMP2 p.Ala103Thr Uncertain significance ★★ ⚠ same type
BMP2 p.Ala106Thr 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/bmp2-p-his97arg (accessed [today's date]).

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