Is BMPR2 p.Arg357Lys (c.1070G>A) pathogenic?

BMPR2 p.Arg357Lys (c.1070G>A) is classified Uncertain significance in BMPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-12). AlphaMissense: likely benign (0.0632); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with BMPR2 p.Arg357Lys (c.1070G>A)?

BMPR2 p.Arg357Lys (c.1070G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPR2 p.Arg357Lys (c.1070G>A) in the general population?

BMPR2 p.Arg357Lys (c.1070G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BMPR2 p.Arg357Lys (c.1070G>A)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg357Lys

c.1070G>A · rs1574493769 · VCV1783333

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -4.59	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 5.2	GERP -1.1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	16.45	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 0.00167% Admixed American · 1/60,018 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000479% 7/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000424%	236,004

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: BMPR2
Protein: p.Arg357Lys
Coding: c.1070G>A
MANE Select: NM_001204
dbSNP: rs1574493769
Type: single nucleotide variant
Location: chr2:202530896 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 357: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain; a UniProt-annotated variant site (in pph1; loss of localization to the plasma membrane; localized to the cytoplasm)

Full BMPR2 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

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BMPR2 p.Asn588Ser Uncertain significance ★★ ⚠ same condition
BMPR2 p.Asp682Glu Uncertain significance ★★ ⚠ same condition
BMPR2 p.Gln834Arg Uncertain significance ★★ ⚠ same condition
BMPR2 p.Glu31Lys Uncertain significance ★★ ⚠ same condition
BMPR2 p.His324Arg 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/bmpr2-p-arg357lys (accessed [today's date]).

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