MPL p.Thr487=
c.1461C>A · rs967998969 · VCV2926026
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0313%, eas)
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 -14 | GERP -3.4 |
| Overall | ||
| CADD | 0.337 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0313%
East Asian · 13/41,540 alleles
Filtering AF
0.0185%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.0011%
17/1,552,102 alleles · ultra-rare
exomes 15/1,399,968 · genomes 2/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0313% | 3,195 |
| European (non-Finnish) | 0.000347% | 287,909 |
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.Thr487=
- Coding
- c.1461C>A
- MANE Select
- NM_005373
- dbSNP
- rs967998969
- Type
- single nucleotide variant
- Location
- chr1:43348995 (GRCh38)
- Gene constraint
- LOEUF 1.022 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.44 · 1 PDB
Similar variants
- MPL p.Thr487Ile Uncertain significance ★ ⚠ 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-thr487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown