Is BMPR2 p.Arg213Gln (c.638G>A) pathogenic?

BMPR2 p.Arg213Gln (c.638G>A) is classified Uncertain significance in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely pathogenic (0.866); Very rare (popmax 0.00415%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BMPR2 p.Arg213Gln (c.638G>A)?

BMPR2 p.Arg213Gln (c.638G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPR2 p.Arg213Gln (c.638G>A) in the general population?

BMPR2 p.Arg213Gln (c.638G>A) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about BMPR2 p.Arg213Gln (c.638G>A)?

AlphaMissense predicts likely pathogenic (score 0.866) — an in-silico prediction, not a clinical call.

BMPR2 p.Arg213Gln

c.638G>A · rs763757383 · VCV2282718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.866	likely pathogenic
REVEL	0.721	pathogenic-leaning
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% European (non-Finnish) · 49/1,180,030 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00341% 55/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,082
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,904

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.Arg213Gln
Coding: c.638G>A
MANE Select: NM_001204
dbSNP: rs763757383
Type: single nucleotide variant
Location: chr2:202518838 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 213: a binding site; the protein kinase domain

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

BMPR2 p.Arg213= Likely benign ★ same residue
BMPR2 p.Arg213Ter Pathogenic ★★ same residue
BMPR2 p.Ala35Val Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg114His Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg357Lys Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg857Trp Uncertain significance ★★ ⚠ same condition
BMPR2 p.Asn588Ser Uncertain significance ★★ ⚠ same condition
BMPR2 p.Asp682Glu 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-arg213gln (accessed [today's date]).

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