Is BMPR2 p.Val429Ile (c.1285G>A) pathogenic?

BMPR2 p.Val429Ile (c.1285G>A) is classified Conflicting classifications of pathogenicity in BMPR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.0828); Ultra-rare (popmax 0.0383%, amr); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Val429Ile (c.1285G>A)?

BMPR2 p.Val429Ile (c.1285G>A) is associated with Primary pulmonary hypertension, pulmonary venoocclusive disease 1, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Val429Ile (c.1285G>A) in the general population?

BMPR2 p.Val429Ile (c.1285G>A) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

What do computational predictors say about BMPR2 p.Val429Ile (c.1285G>A)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

BMPR2 p.Val429Ile

c.1285G>A · VCV3481265

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -7.74	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 7.6	GERP 0.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 20 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	23.2	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 0.0383% Admixed American · 23/59,984 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00613% 99/1,613,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,608
Middle Eastern	0.033%	3,028
European (non-Finnish)	0.00576%	17,351
South Asian	0.00329%	30,354
African / African-American	0.00267%	37,492
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Val429Ile
Coding: c.1285G>A
MANE Select: NM_001204
Type: single nucleotide variant
Location: chr2:202542319 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 429: 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

Primary pulmonary hypertension — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pulmonary venoocclusive disease 1 pulmonary hypertension, primary, 1

Similar variants

BMPR2 p.Val429fs Likely pathogenic ★ same residue
BMPR2 p.Val429_Gln437delinsGlu Uncertain significance ★ same residue
BMPR2 c.1276+3A>G Likely pathogenic ★★★ same condition
BMPR2 c.1276+3A>T Likely pathogenic ★★★ same condition
BMPR2 c.1276+4A>G Likely pathogenic ★★★ same condition
BMPR2 c.1277-8A>G Pathogenic ★★★ same condition
BMPR2 c.1277-9A>G Pathogenic ★★★ same condition
BMPR2 c.1413+1G>A Pathogenic ★★★ 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-val429ile (accessed [today's date]).

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