Is BMPR2 p.Ile257= (c.771T>C) pathogenic?

BMPR2 p.Ile257= (c.771T>C) is classified Likely benign in BMPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). Absent from gnomAD v4.1; Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Ile257= (c.771T>C)?

BMPR2 p.Ile257= (c.771T>C) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Ile257= (c.771T>C) in the general population?

BMPR2 p.Ile257= (c.771T>C) is absent from gnomAD v4.1 (gnomAD).

BMPR2 p.Ile257=

c.771T>C · rs2106007050 · VCV1530336

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Primary pulmonary hypertension

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 0.043	GERP -2.7, phastCons 0.97
Overall
CADD	7.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMPR2
Protein: p.Ile257=
Coding: c.771T>C
MANE Select: NM_001204
dbSNP: rs2106007050
Type: single nucleotide variant
Location: chr2:202518971 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 257: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); the protein kinase domain

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.Ile257Val Uncertain significance ★★ ⚠ same residue
BMPR2 p.Ile257Thr 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-ile257 (accessed [today's date]).

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