Is BMPR2 p.Gly968Arg (c.2902G>C) pathogenic?

BMPR2 p.Gly968Arg (c.2902G>C) is classified Uncertain significance in BMPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-06). AlphaMissense: likely pathogenic (0.5898); Absent from gnomAD v4.1; Associated with BMPR2-related disorder.

What condition is associated with BMPR2 p.Gly968Arg (c.2902G>C)?

BMPR2 p.Gly968Arg (c.2902G>C) is associated with BMPR2-related disorder (ClinVar).

How common is BMPR2 p.Gly968Arg (c.2902G>C) in the general population?

BMPR2 p.Gly968Arg (c.2902G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMPR2 p.Gly968Arg (c.2902G>C)?

AlphaMissense predicts likely pathogenic (score 0.5898) — an in-silico prediction, not a clinical call.

BMPR2 p.Gly968Arg

c.2902G>C · rs2468751109 · VCV2630689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BMPR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.5898	likely pathogenic
REVEL	0.556	indeterminate
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,896 bp · p 0.061 · regional, not allelic
Overall
CADD	29.1	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

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.Gly968Arg
Coding: c.2902G>C
MANE Select: NM_001204
dbSNP: rs2468751109
Type: single nucleotide variant
Location: chr2:202559731 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.07 · 7 PDB
Residue 968: 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); the 'disordered' region

Full BMPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BMPR2-related disorder

Similar variants

BMPR2 p.Gly968Asp Uncertain significance ★ ⚠ same residue
BMPR2 p.Arg321Ter Pathogenic ★★ same condition
BMPR2 p.Arg332Ter Pathogenic ★★ same condition
BMPR2 p.Arg591Ter Pathogenic/Likely pathogenic ★★ same condition
BMPR2 p.Arg597Ter Pathogenic ★★ same condition
BMPR2 p.Cys117Tyr Pathogenic/Likely pathogenic ★★ same condition
BMPR2 p.Gln741Ter Pathogenic/Likely pathogenic ★★ same condition
BMPR2 p.Tyr67Cys 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-gly968arg (accessed [today's date]).

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