Is MPL p.Leu38= (c.114G>A) pathogenic?

MPL p.Leu38= (c.114G>A) is classified Uncertain significance in MPL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-24). Absent from gnomAD v4.1; Associated with congenital amegakaryocytic thrombocytopenia.

What condition is associated with MPL p.Leu38= (c.114G>A)?

MPL p.Leu38= (c.114G>A) is associated with congenital amegakaryocytic thrombocytopenia (ClinVar).

How common is MPL p.Leu38= (c.114G>A) in the general population?

MPL p.Leu38= (c.114G>A) is absent from gnomAD v4.1 (gnomAD).

MPL p.Leu38=

c.114G>A · VCV4057883

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital amegakaryocytic thrombocytopenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.39	acceptor loss, 13 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.7	GERP 0.66, phastCons 1
Overall
CADD	12.15	PHRED · no single calibrated threshold — expert panels disagree

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: MPL
Protein: p.Leu38=
Coding: c.114G>A
MANE Select: NM_005373
Type: single nucleotide variant
Location: chr1:43338133 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.44 · 1 PDB
Residue 38: a β-strand

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

Disease context

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

Similar variants

MPL c.1165+1G>C Likely pathogenic ★★ same condition
MPL c.1166-1G>C Likely pathogenic ★★ same condition
MPL c.1468+2T>C Pathogenic/Likely pathogenic ★★ same condition
MPL c.1469-2A>T Pathogenic/Likely pathogenic ★★ same condition
MPL c.1566-1G>A Likely pathogenic ★★ same condition
MPL c.1653+1G>C Likely pathogenic ★★ same condition
MPL c.79+2T>A Pathogenic/Likely pathogenic ★★ same condition
MPL c.853+1G>A 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/mpl-p-leu38 (accessed [today's date]).

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