Is MPL p.Arg102= (c.306T>A) pathogenic?

MPL p.Arg102= (c.306T>A) is classified Likely benign in MPL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-27). Absent from gnomAD v4.1; Associated with congenital amegakaryocytic thrombocytopenia.

How common is MPL p.Arg102= (c.306T>A) in the general population?

MPL p.Arg102= (c.306T>A) is absent from gnomAD v4.1 (gnomAD).

MPL p.Arg102=

Q: What condition is associated with MPL p.Arg102= (c.306T>A)?

MPL p.Arg102= (c.306T>A) is associated with congenital amegakaryocytic thrombocytopenia, essential thrombocythemia (ClinVar).

c.306T>A · rs140354935 · VCV1160441

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -1.9	GERP -3.8
Overall
CADD	6.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPL
Protein: p.Arg102=
Coding: c.306T>A
MANE Select: NM_005373
dbSNP: rs140354935
Type: single nucleotide variant
Location: chr1:43338635 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.44 · 1 PDB
Residue 102: a UniProt-annotated variant site (in camt1); a UniProt-annotated variant site (in camt1; loss of function; loss of membrane localization, impaired glycosylation)

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 p.Arg102Cys Pathogenic/Likely pathogenic ★★ same residue
MPL p.Arg102Pro Pathogenic ★★ ⚠ same residue
MPL p.Arg102His 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

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-arg102 (accessed [today's date]).

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