Is BMPR2 p.Cys66= (c.198C>T) pathogenic?

BMPR2 p.Cys66= (c.198C>T) is classified Uncertain significance in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with pulmonary hypertension, primary, 1.

What condition is associated with BMPR2 p.Cys66= (c.198C>T)?

BMPR2 p.Cys66= (c.198C>T) is associated with pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Cys66= (c.198C>T) in the general population?

BMPR2 p.Cys66= (c.198C>T) is absent from gnomAD v4.1 (gnomAD).

BMPR2 p.Cys66=

c.198C>T · rs1692290741 · VCV896820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pulmonary hypertension, primary, 1

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 0.63	GERP 0.16, phastCons 1
Overall
CADD	7.614	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.Cys66=
Coding: c.198C>T
MANE Select: NM_001204
dbSNP: rs1692290741
Type: single nucleotide variant
Location: chr2:202464930 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 66: a disulfide bond; a β-strand

Full BMPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pulmonary hypertension, primary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPR2 p.Cys66Arg Pathogenic same residue
BMPR2 p.Cys66Gly Pathogenic same residue
BMPR2 p.Cys66Tyr Pathogenic 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

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-cys66 (accessed [today's date]).

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