Is MPL p.Val366fs (c.1095del) pathogenic?

MPL p.Val366fs (c.1095del) is classified Likely pathogenic in MPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-25). Associated with congenital amegakaryocytic thrombocytopenia 1.

What condition is associated with MPL p.Val366fs (c.1095del)?

MPL p.Val366fs (c.1095del) is associated with congenital amegakaryocytic thrombocytopenia 1, primary myelofibrosis, thrombocythemia 2 (ClinVar).

How is Congenital amegakaryocytic thrombocytopenia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MPL p.Val366fs

c.1095del · VCV3584344

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

congenital amegakaryocytic thrombocytopenia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1

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

Variant & gene context

Gene: MPL
Protein: p.Val366fs
Coding: c.1095del
MANE Select: NM_005373
Type: Deletion
Location: chr1:43346558 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.44 · 1 PDB
Residue 366: a β-strand

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

Disease context

congenital amegakaryocytic thrombocytopenia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary myelofibrosis thrombocythemia 2

For Congenital amegakaryocytic thrombocytopenia (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

MPL c.1653+1del Pathogenic/Likely pathogenic ★★ same condition
MPL p.Arg325fs Pathogenic/Likely pathogenic ★★ same condition
MPL p.Cys77fs Pathogenic/Likely pathogenic ★★ same condition
MPL p.Leu103fs Pathogenic/Likely pathogenic ★★ same condition
MPL p.Leu79fs Pathogenic ★★ same condition
MPL p.Phe126fs Pathogenic ★★ same condition
MPL p.Pro70fs Pathogenic/Likely pathogenic ★★ same condition
MPL p.Val366Ala Uncertain significance ★★ ⚠ same residue

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/mpl-p-val366fs (accessed [today's date]).

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