Is BMPR1B p.Ser183Pro (c.547T>C) pathogenic?

BMPR1B p.Ser183Pro (c.547T>C) is classified Uncertain significance in BMPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-27). AlphaMissense: likely pathogenic (0.7758); Very rare (popmax 0.00223%, eas); Associated with Pulmonary arterial hypertension associated with congenital heart disease.

What condition is associated with BMPR1B p.Ser183Pro (c.547T>C)?

BMPR1B p.Ser183Pro (c.547T>C) is associated with Pulmonary arterial hypertension associated with congenital heart disease (ClinVar).

How common is BMPR1B p.Ser183Pro (c.547T>C) in the general population?

BMPR1B p.Ser183Pro (c.547T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BMPR1B p.Ser183Pro (c.547T>C)?

AlphaMissense predicts likely pathogenic (score 0.7758) — an in-silico prediction, not a clinical call.

BMPR1B p.Ser183Pro

c.547T>C · rs141691706 · VCV548684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7758 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Pulmonary arterial hypertension associated with congenital heart disease

Computational evidence

Protein change
AlphaMissense	0.7758	likely pathogenic
REVEL	0.751	pathogenic-leaning
SaProt	LLR -11.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 25 kb · p 0.048 · regional, not allelic
Overall
CADD	28.3	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

Grpmax group 0.00223% East Asian · 1/44,872 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00112% 18/1,613,704 alleles · very rare exomes 15/1,461,568 · genomes 3/152,136 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,825
East Asiangrpmax	0.00223%	44,872
South Asian	0.0022%	45,540
European (non-Finnish)	0.00102%	98,320

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BMPR1B
Protein: p.Ser183Pro
Coding: c.547T>C
MANE Select: NM_001203
dbSNP: rs141691706
Type: single nucleotide variant
Location: chr4:95125083 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 183: an α-helix; the gs domain

Full BMPR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Pulmonary arterial hypertension associated with congenital heart disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPR1B c.585+1G>C Likely pathogenic ★★ same type
BMPR1B p.Arg486Trp Pathogenic ★★ same type
BMPR1B c.*828T>G Uncertain significance ★★ same type
BMPR1B c.*83C>G Uncertain significance ★★ same type
BMPR1B p.Arg214His Uncertain significance ★★ ⚠ same type
BMPR1B p.Arg26Pro Uncertain significance ★★ ⚠ same type
BMPR1B p.Arg412Gly Uncertain significance ★★ ⚠ same type
BMPR1B p.Arg91Ile Uncertain significance ★★ ⚠ same type

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/bmpr1b-p-ser183pro (accessed [today's date]).

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