Is MPL p.Asp53= (c.159T>C) pathogenic?

MPL p.Asp53= (c.159T>C) is classified Likely benign in MPL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). Very rare (popmax 0.00401%, afr); Associated with congenital amegakaryocytic thrombocytopenia.

How common is MPL p.Asp53= (c.159T>C) in the general population?

MPL p.Asp53= (c.159T>C) is very rare (popmax 0.00401%, afr) (gnomAD).

MPL p.Asp53=

Q: What condition is associated with MPL p.Asp53= (c.159T>C)?

MPL p.Asp53= (c.159T>C) is associated with congenital amegakaryocytic thrombocytopenia, essential thrombocythemia (ClinVar).

c.159T>C · rs753950108 · VCV2951765

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

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 0.71	GERP 0.99, phastCons 0.99
Overall
CADD	8.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,902 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,016 alleles · very rare exomes 2/1,461,880 · genomes 2/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,967
European (non-Finnish)	8.47e-05%	1,180,030

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.Asp53=
Coding: c.159T>C
MANE Select: NM_005373
dbSNP: rs753950108
Type: single nucleotide variant
Location: chr1:43338178 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.44 · 1 PDB
Residue 53: 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

Also linked: essential thrombocythemia

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-asp53 (accessed [today's date]).

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