MPL p.Glu337=
c.1011A>G · rs1318577614 · VCV1543080
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
congenital amegakaryocytic thrombocytopenia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.64 | GERP -2.9, phastCons 0.99 |
| Overall | ||
| CADD | 3.977 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,012 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00041%
6/1,461,830 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,012 |
| African / African-American | 0.00133% | 75,030 |
| European (non-Finnish) | 0.000339% | 294,990 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MPL
- Protein
- p.Glu337=
- Coding
- c.1011A>G
- MANE Select
- NM_005373
- dbSNP
- rs1318577614
- Type
- single nucleotide variant
- Location
- chr1:43346475 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.44 · 1 PDB
- Residue 337
- a disulfide bond
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-glu337 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown