Is BMPR2 p.Cys60= (c.180C>T) pathogenic?

BMPR2 p.Cys60= (c.180C>T) is classified Likely benign in BMPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-21). Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BMPR2 p.Cys60= (c.180C>T)?

BMPR2 p.Cys60= (c.180C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BMPR2 p.Cys60= (c.180C>T) in the general population?

BMPR2 p.Cys60= (c.180C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

BMPR2 p.Cys60=

c.180C>T · rs2105959771 · VCV1157657

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.69	GERP -5.3, phastCons 0.011
Overall
CADD	7.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,020 alleles · very rare exomes 2/1,461,844 · genomes 0/152,176 · joint denominator

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.Cys60=
Coding: c.180C>T
MANE Select: NM_001204
dbSNP: rs2105959771
Type: single nucleotide variant
Location: chr2:202464912 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 60: a disulfide bond; a UniProt-annotated variant site (in pph1; loss of function in bmp signaling pathway via smad proteins activation; does not localize to the cell surface; when transfected in epithelial cells it results in constitutive p38mapk phosphorylation consistent with a gain of function in the activation of p38mapk cascade)

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.Cys60Phe Uncertain significance ★ ⚠ same residue
BMPR2 p.Cys60Ser Uncertain significance ★ ⚠ same residue
BMPR2 p.Cys60Arg Pathogenic same residue
BMPR2 p.Cys60Gly Pathogenic same residue
BMPR2 p.Cys60Tyr Pathogenic same residue
BMPR2 p.Ala35Val Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg114His Uncertain significance ★★ ⚠ same condition
BMPR2 p.Arg357Lys 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-cys60 (accessed [today's date]).

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