MPL p.Pro106=
c.318G>A · rs370001905 · VCV699866
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0213%, afr)
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 -5.8 | GERP -3.8 |
| Overall | ||
| CADD | 0.887 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0213%
African / African-American · 16/74,996 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.00297%
48/1,614,028 alleles · ultra-rare
exomes 36/1,461,884 · genomes 12/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0213% | 4,687 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.0117% | 8,574 |
| East Asian | 0.00892% | 11,214 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| South Asian | 0.0022% | 45,533 |
| European (non-Finnish) | 0.00136% | 73,750 |
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.Pro106=
- Coding
- c.318G>A
- MANE Select
- NM_005373
- dbSNP
- rs370001905
- Type
- single nucleotide variant
- Location
- chr1:43338647 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.44 · 1 PDB
- Residue 106
- a UniProt-annotated variant site (in thcyt2; gain of function; loss of membrane localization, impaired glycosylation); a β-strand
Similar variants
- MPL p.Pro106Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro106 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown