Is BMPR2 p.Trp85Arg (c.253T>C) pathogenic?

BMPR2 p.Trp85Arg (c.253T>C) is classified Uncertain significance in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely pathogenic (0.9974); Absent from gnomAD v4.1; Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Trp85Arg (c.253T>C)?

BMPR2 p.Trp85Arg (c.253T>C) is associated with Primary pulmonary hypertension (ClinVar).

How common is BMPR2 p.Trp85Arg (c.253T>C) in the general population?

BMPR2 p.Trp85Arg (c.253T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR2 p.Trp85Arg (c.253T>C)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

BMPR2 p.Trp85Arg

c.253T>C · rs2469645103 · VCV2812636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic · top 3% in BMPR2
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -13.90	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Trp85Arg
Coding: c.253T>C
MANE Select: NM_001204
dbSNP: rs2469645103
Type: single nucleotide variant
Location: chr2:202467524 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB

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.Trp85Ter Pathogenic ★ 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
BMPR2 p.Arg491Trp 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-trp85arg (accessed [today's date]).

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