Is BMP2 p.Val74fs (c.217_218dup) pathogenic?

BMP2 p.Val74fs (c.217218dup) is classified Pathogenic in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). Associated with short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies.

BMP2 p.Val74fs

Q: What condition is associated with BMP2 p.Val74fs (c.217_218dup)?

BMP2 p.Val74fs (c.217_218dup) is associated with short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (ClinVar).

c.217_218dup · VCV3384676

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 0.46, phastCons 1

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

Variant & gene context

Gene: BMP2
Protein: p.Val74fs
Coding: c.217_218dup
MANE Select: NM_001200
Type: Duplication
Location: chr20:6770341 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 74: a UniProt-annotated variant site (in ssfsc1)

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

Disease context

short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Cys329Ter Likely pathogenic ★★ same condition
BMP2 p.Arg190Ser Benign ★★ same condition
BMP2 p.Ser87= Benign ★★ same condition
BMP2 p.Glu205Ter Pathogenic ★ same condition
BMP2 p.Glu27Ter Likely pathogenic ★ same condition
BMP2 p.Trp313Ter 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/bmp2-p-val74fs (accessed [today's date]).

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