Is BMP2 p.Arg6Pro (c.17G>C) pathogenic?

BMP2 p.Arg6Pro (c.17G>C) is classified Uncertain significance in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-02). AlphaMissense: likely benign (0.2192); Very rare (popmax 0.00952%, afr).

How common is BMP2 p.Arg6Pro (c.17G>C) in the general population?

BMP2 p.Arg6Pro (c.17G>C) is very rare (popmax 0.00952%, afr) (gnomAD).

What do computational predictors say about BMP2 p.Arg6Pro (c.17G>C)?

AlphaMissense predicts likely benign (score 0.2192) — an in-silico prediction, not a clinical call.

BMP2 p.Arg6Pro

c.17G>C · VCV3610416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00952%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2192	likely benign
REVEL	0.612	indeterminate
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 8,670 bp · p 0.13 · regional, not allelic
Overall
CADD	26.2	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 0.00952% African / African-American · 7/73,514 alleles

Filtering AF 0.00445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.000708% 11/1,553,180 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00952%	10,502
South Asian	0.00353%	28,319
Admixed American	0.00189%	52,842

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.Arg6Pro
Coding: c.17G>C
MANE Select: NM_001200
Type: single nucleotide variant
Location: chr20:6770143 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB

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

Similar variants

BMP2 p.Arg6Cys Uncertain significance ★★ ⚠ same residue
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

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-arg6pro (accessed [today's date]).

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