Is MPIG6B p.Pro191= (c.573A>G) pathogenic?

MPIG6B p.Pro191= (c.573A>G) is classified Uncertain significance in MPIG6B (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-05). Ultra-rare (popmax 0.0368%, nfe); Associated with thrombocytopenia, anemia, and myelofibrosis.

What condition is associated with MPIG6B p.Pro191= (c.573A>G)?

MPIG6B p.Pro191= (c.573A>G) is associated with thrombocytopenia, anemia, and myelofibrosis (ClinVar).

How common is MPIG6B p.Pro191= (c.573A>G) in the general population?

MPIG6B p.Pro191= (c.573A>G) is ultra-rare (popmax 0.0368%, nfe) (gnomAD).

MPIG6B p.Pro191=

c.573A>G · VCV3602678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0368%, nfe)

Conditions

thrombocytopenia, anemia, and myelofibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.77
Overall
CADD	6.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0368% European (non-Finnish) · 434/1,179,958 alleles

Filtering AF 0.0339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.0291% 469/1,613,946 alleles · ultra-rare exomes 440/1,461,872 · genomes 29/152,074 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0368%	2,719
Middle Eastern	0.033%	3,030
Admixed American	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0176%	5,683
African / African-American	0.00534%	18,740
Finnishnot grpmax-eligible	0.00156%	63,994
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: MPIG6B
Protein: p.Pro191=
Coding: c.573A>G
MANE Select: NM_138272
Type: single nucleotide variant
Location: chr6:31724796 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 1 PDB
Residue 191: a UniProt-annotated variant site (in thamy; increased protein degradation; decreased enhancement of hematopoietic lineage differentiation)

Full MPIG6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombocytopenia, anemia, and myelofibrosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPIG6B p.Arg175Ter Pathogenic/Likely pathogenic ★★ same condition
MPIG6B p.Cys108Ter Pathogenic ★★ same condition
MPIG6B p.Thr186= Likely pathogenic ★★ same condition
MPIG6B p.Ala52Thr Uncertain significance ★★ ⚠ same condition
MPIG6B p.Arg83His Uncertain significance ★★ ⚠ same condition
MPIG6B p.Trp163Ter Pathogenic ★ same condition
MPIG6B p.Cys108Phe Uncertain significance ★ ⚠ same condition
MPIG6B p.Pro173Gln Conflicting classifications of pathogenicity ★ ⚠ 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/mpig6b-p-pro191 (accessed [today's date]).

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