Is BMPR2 p.Ile579Val (c.1735A>G) pathogenic?

BMPR2 p.Ile579Val (c.1735A>G) is classified Conflicting classifications of pathogenicity in BMPR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0522); Ultra-rare (popmax 0.0164%, mid); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Ile579Val (c.1735A>G)?

BMPR2 p.Ile579Val (c.1735A>G) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Ile579Val (c.1735A>G) in the general population?

BMPR2 p.Ile579Val (c.1735A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BMPR2 p.Ile579Val (c.1735A>G)?

AlphaMissense predicts likely benign (score 0.0522) — an in-silico prediction, not a clinical call.

BMPR2 p.Ile579Val

c.1735A>G · rs775982546 · VCV2723112

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0522 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.0522	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -5.84	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 -2.3	GERP -4.5
Regional constraint	o/e 0.92	unconstrained · MANE · 6,896 bp · p 0.061 · regional, not allelic
Overall
CADD	0.232	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00347% 56/1,614,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0154%	6,506
African / African-American	0.00934%	10,701
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00263%	38,066

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.Ile579Val
Coding: c.1735A>G
MANE Select: NM_001204
dbSNP: rs775982546
Type: single nucleotide variant
Location: chr2:202555400 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 579: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); 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

Similar variants

BMPR2 p.Ile579Leu Uncertain significance ★ ⚠ same residue
BMPR2 p.Ile579Thr Uncertain significance ★ ⚠ same residue
BMPR2 c.1128+1G>A Pathogenic ★★ same condition
BMPR2 c.1128+1G>C Pathogenic ★★ same condition
BMPR2 c.621+1G>T Pathogenic/Likely pathogenic ★★ same condition
BMPR2 c.853-2A>G Pathogenic ★★ same condition
BMPR2 p.Arg147Ter Pathogenic ★★ same condition
BMPR2 p.Arg213Ter 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-ile579val (accessed [today's date]).

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