Is BMP2 p.Ala343fs (c.1026dup) pathogenic?

BMP2 p.Ala343fs (c.1026dup) is classified Likely pathogenic in BMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). Absent from gnomAD; Associated with BMP2-related disorder.

What condition is associated with BMP2 p.Ala343fs (c.1026dup)?

BMP2 p.Ala343fs (c.1026dup) is associated with BMP2-related disorder (ClinVar).

How common is BMP2 p.Ala343fs (c.1026dup) in the general population?

BMP2 p.Ala343fs (c.1026dup) is absent from gnomAD (gnomAD).

BMP2 p.Ala343fs

c.1026dup · rs2514427113 · VCV2636252

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

BMP2-related disorder

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	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 · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BMP2
Protein: p.Ala343fs
Coding: c.1026dup
MANE Select: NM_001200
dbSNP: rs2514427113
Type: Duplication
Location: chr20:6778923 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.37 · 21 PDB
Residue 343: a disulfide bond; a UniProt-annotated variant site (in ssfsc1); an α-helix

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

Disease context

BMP2-related disorder

Similar variants

BMP2 p.Thr141fs Likely pathogenic ★ same condition
BMP2 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 p.Gln89Ter Pathogenic/Likely pathogenic ★★ same condition
BMP2 c.346+1G>C Likely pathogenic ★ same condition
BMP2 p.Trp204Ter Likely pathogenic ★ same condition
BMP2 p.Val109fs Likely pathogenic same condition
BMP2 p.Ala231Gly Uncertain significance ⚠ same condition
BMP2 p.Glu123Lys Uncertain significance ⚠ 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-ala343fs (accessed [today's date]).

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