Is MPL p.Pro70= (c.210G>A) pathogenic?

MPL p.Pro70= (c.210G>A) is classified Benign/Likely benign in MPL (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.58%, afr); Associated with essential thrombocythemia.

What condition is associated with MPL p.Pro70= (c.210G>A)?

MPL p.Pro70= (c.210G>A) is associated with essential thrombocythemia, congenital amegakaryocytic thrombocytopenia, congenital amegakaryocytic thrombocytopenia 1 (ClinVar).

How common is MPL p.Pro70= (c.210G>A) in the general population?

MPL p.Pro70= (c.210G>A) is low-frequency (popmax 1.58%, afr) (gnomAD).

How is Essential thrombocythemia inherited?

Typically Multigenic/multifactorial, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

MPL p.Pro70=

c.210G>A · rs6086 · VCV211522

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.58%, afr)

Conditions

essential thrombocythemia

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 -0.012	GERP -4.1
Overall
CADD	9.807	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.58% African / African-American · 1,182/74,990 alleles

Filtering AF 1.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.47%

Overall 0.0833% 1,344/1,613,632 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.58%	63
Remaining individualsnot grpmax-eligible	0.11%	906
Middle Eastern	0.104%	962
Admixed American	0.09%	1,111
European (non-Finnish)	0.00263%	38,065
East Asian	0.00223%	44,870
South Asian	0.0011%	91,072

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.Pro70=
Coding: c.210G>A
MANE Select: NM_005373
dbSNP: rs6086
Type: single nucleotide variant
Location: chr1:43338229 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.44 · 1 PDB
Residue 70: a β-strand

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

Disease context

essential thrombocythemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital amegakaryocytic thrombocytopenia congenital amegakaryocytic thrombocytopenia 1

For Essential thrombocythemia (Orphanet):

Inheritance: Multigenic/multifactorial, Not applicable
Onset: All ages
Prevalence: 1-5 / 10 000 (United States)

Similar variants

MPL p.Pro70Leu Likely benign ★★ same residue
MPL p.Pro70fs Pathogenic/Likely pathogenic ★★ 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

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-pro70 (accessed [today's date]).

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