Is BMPR2 p.Glu439= (c.1317G>A) pathogenic?

BMPR2 p.Glu439= (c.1317G>A) is classified Likely benign in BMPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-12). Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with BMPR2 p.Glu439= (c.1317G>A)?

BMPR2 p.Glu439= (c.1317G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BMPR2 p.Glu439= (c.1317G>A) in the general population?

BMPR2 p.Glu439= (c.1317G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

BMPR2 p.Glu439=

c.1317G>A · rs150555588 · VCV1134430

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -1.2, phastCons 1
Overall
CADD	5.949	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Overall 0.000248% 4/1,613,904 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,240
East Asiangrpmax	0.00223%	44,874
European (non-Finnish)	8.47e-05%	1,179,986

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu439=
Coding: c.1317G>A
MANE Select: NM_001204
dbSNP: rs150555588
Type: single nucleotide variant
Location: chr2:202542351 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 439: an α-helix; 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

BMPR2 p.Glu439Asp Uncertain significance ★ ⚠ 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
BMPR2 p.Gln834Arg 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-glu439 (accessed [today's date]).

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