Is BMPR1A p.Pro140Arg (c.419C>G) pathogenic?

BMPR1A p.Pro140Arg (c.419C>G) is classified Uncertain significance in BMPR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). AlphaMissense: likely benign (0.2251); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BMPR1A p.Pro140Arg (c.419C>G)?

BMPR1A p.Pro140Arg (c.419C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BMPR1A p.Pro140Arg (c.419C>G) in the general population?

BMPR1A p.Pro140Arg (c.419C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR1A p.Pro140Arg (c.419C>G)?

AlphaMissense predicts likely benign (score 0.2251) — an in-silico prediction, not a clinical call.

BMPR1A p.Pro140Arg

c.419C>G · rs1312138101 · VCV2626636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2251	likely benign
REVEL	0.746	pathogenic-leaning
SaProt	LLR -12.35	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 27 kb · p 2.2e-08 · regional, not allelic
Overall
CADD	32.0	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

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: BMPR1A
Protein: p.Pro140Arg
Coding: c.419C>G
MANE Select: NM_004329
dbSNP: rs1312138101
Type: single nucleotide variant
Location: chr10:86899879 (GRCh38)
Gene constraint: LOEUF 0.195 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.86 · 11 PDB
Residue 140: an α-helix

Full BMPR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPR1A p.Pro140Ala Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro140Leu Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro140Ser Uncertain significance ★★ ⚠ same residue
BMPR1A p.Pro140fs Pathogenic ★★ same residue
BMPR1A c.1166+1G>A Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>A Pathogenic/Likely pathogenic ★★ same condition
BMPR1A c.1473+1G>C Pathogenic/Likely pathogenic ★★ same condition
BMPR1A c.230+1G>A Likely 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/bmpr1a-p-pro140arg (accessed [today's date]).

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