Is BMP2 p.Arg154Ter (c.460C>T) pathogenic?

BMP2 p.Arg154Ter (c.460C>T) is classified Pathogenic/Likely pathogenic in BMP2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-11-25). Absent from gnomAD v4.1; Associated with BMP2-related disorder.

What condition is associated with BMP2 p.Arg154Ter (c.460C>T)?

BMP2 p.Arg154Ter (c.460C>T) is associated with BMP2-related disorder, short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (ClinVar).

How common is BMP2 p.Arg154Ter (c.460C>T) in the general population?

BMP2 p.Arg154Ter (c.460C>T) is absent from gnomAD v4.1 (gnomAD).

BMP2 p.Arg154Ter

c.460C>T · rs1057523275 · VCV388927

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

BMP2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: BMP2
Protein: p.Arg154Ter
Coding: c.460C>T
MANE Select: NM_001200
dbSNP: rs1057523275
Type: single nucleotide variant
Location: chr20:6778358 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 154: a UniProt-annotated variant site (in ssfsc1)

Full BMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BMP2-related disorder

Also linked: short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies

Similar variants

BMP2 p.Arg154Gln Uncertain significance ★ same residue
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Cys329Ter Likely pathogenic ★★ same condition
BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Arg190Ser Benign ★★ same condition
BMP2 p.Ser87= Benign ★★ same condition
BMP2 c.346+1G>C Likely pathogenic ★ same condition
BMP2 p.Glu205Ter 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/bmp2-p-arg154ter (accessed [today's date]).

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