Is BMPR2 p.Ser61Leu (c.182C>T) pathogenic?

BMPR2 p.Ser61Leu (c.182C>T) is classified Conflicting classifications of pathogenicity in BMPR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-22). AlphaMissense: likely benign (0.1011); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with BMPR2 p.Ser61Leu (c.182C>T)?

BMPR2 p.Ser61Leu (c.182C>T) is associated with Inborn genetic diseases, pulmonary venoocclusive disease 1, pulmonary hypertension, primary, 1 (ClinVar).

How common is BMPR2 p.Ser61Leu (c.182C>T) in the general population?

BMPR2 p.Ser61Leu (c.182C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BMPR2 p.Ser61Leu (c.182C>T)?

AlphaMissense predicts likely benign (score 0.1011) — an in-silico prediction, not a clinical call.

BMPR2 p.Ser61Leu

c.182C>T · rs1166280962 · VCV2138218

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1011 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1011	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 153 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	24.2	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 0.00267% African / African-American · 2/74,964 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000616% 9/1,461,850 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,482
European (non-Finnish)	0.000593%	168,573

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.Ser61Leu
Coding: c.182C>T
MANE Select: NM_001204
dbSNP: rs1166280962
Type: single nucleotide variant
Location: chr2:202464914 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 61: a disulfide bond

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

Also linked: pulmonary venoocclusive disease 1 pulmonary hypertension, primary, 1

Similar variants

BMPR2 p.Ser61Ala Uncertain significance ★ ⚠ same residue
BMPR2 p.Ser61Trp 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
BMPR2 c.1277-9A>G Pathogenic ★★★ same condition
BMPR2 c.1413+1G>A 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-ser61leu (accessed [today's date]).

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