Is BMPR2 p.Ala714Ser (c.2140G>T) pathogenic?

BMPR2 p.Ala714Ser (c.2140G>T) is classified Conflicting classifications of pathogenicity in BMPR2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-23). AlphaMissense: likely benign (0.2268); Ultra-rare (popmax 0.08%, afr); Associated with Primary pulmonary hypertension.

What condition is associated with BMPR2 p.Ala714Ser (c.2140G>T)?

BMPR2 p.Ala714Ser (c.2140G>T) is associated with Primary pulmonary hypertension, pulmonary arterial hypertension (ClinVar).

How common is BMPR2 p.Ala714Ser (c.2140G>T) in the general population?

BMPR2 p.Ala714Ser (c.2140G>T) is ultra-rare (popmax 0.08%, afr) (gnomAD).

What do computational predictors say about BMPR2 p.Ala714Ser (c.2140G>T)?

AlphaMissense predicts likely benign (score 0.2268) — an in-silico prediction, not a clinical call.

BMPR2 p.Ala714Ser

c.2140G>T · rs149067277 · VCV1339416

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2268 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.08%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Primary pulmonary hypertension

Computational evidence

Protein change
AlphaMissense	0.2268	likely benign
REVEL	0.588	indeterminate
SaProt	LLR -4.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,896 bp · p 0.061 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.08% African / African-American · 60/75,030 alleles

Filtering AF 0.0637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0579%

Overall 0.00558% 90/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.08%	1,251
Admixed American	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0192%	5,209
South Asian	0.00659%	15,180

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.Ala714Ser
Coding: c.2140G>T
MANE Select: NM_001204
dbSNP: rs149067277
Type: single nucleotide variant
Location: chr2:202555805 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 714: a UniProt-annotated variant site (in pph1; changed localization to the plasma membrane); a UniProt-annotated variant site (in pph1; loss of localization to the plasma membrane; localized to the cytoplasm)

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

Also linked: pulmonary arterial hypertension

Similar variants

BMPR2 p.Ala714= Likely benign ★ same residue
BMPR2 p.Ala714Gly Uncertain significance ★ ⚠ same residue
BMPR2 p.Ala714Pro Uncertain significance ★ ⚠ same residue
BMPR2 p.Ala714Thr Uncertain significance ★ ⚠ 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

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-ala714ser (accessed [today's date]).

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