Is MPIG6B p.Pro207= (c.621G>T) pathogenic?

MPIG6B p.Pro207= (c.621G>T) is classified Uncertain significance in MPIG6B (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-27). Ultra-rare (popmax 0.0186%, nfe); Associated with thrombocytopenia.

What condition is associated with MPIG6B p.Pro207= (c.621G>T)?

MPIG6B p.Pro207= (c.621G>T) is associated with thrombocytopenia (ClinVar).

How common is MPIG6B p.Pro207= (c.621G>T) in the general population?

MPIG6B p.Pro207= (c.621G>T) is ultra-rare (popmax 0.0186%, nfe) (gnomAD).

MPIG6B p.Pro207=

c.621G>T · rs147600887 · VCV988872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0186%, nfe)

Conditions

thrombocytopenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.216	benign-leaning
Splicing
SpliceAI	Δ0.30	donor loss · deltas
Pangolin	Δ0.43	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.2	GERP 1.4, phastCons 1
Overall
CADD	18.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0186% European (non-Finnish) · 220/1,179,916 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.016% 259/1,613,774 alleles · ultra-rare exomes 239/1,461,794 · genomes 20/151,980 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0437%	2,286
European (non-Finnish)grpmax	0.0186%	5,363
Remaining individualsnot grpmax-eligible	0.0096%	10,413
African / African-American	0.00668%	14,966

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro207=
Coding: c.621G>T
MANE Select: NM_138272
dbSNP: rs147600887
Type: single nucleotide variant
Location: chr6:31724844 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 1 PDB
Residue 207: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPIG6B p.Trp44Cys Uncertain significance ⚠ same condition
MPIG6B p.Arg175Ter Pathogenic/Likely pathogenic ★★ same type
MPIG6B p.Cys108Ter Pathogenic ★★ same type
MPIG6B p.Thr186= Likely pathogenic ★★ same type
MPIG6B c.542-9C>G Uncertain significance ★★ same type
MPIG6B p.Ala21Gly Uncertain significance ★★ ⚠ same type
MPIG6B p.Ala52Thr Uncertain significance ★★ ⚠ same type
MPIG6B p.Arg83His Uncertain significance ★★ ⚠ same type

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-pro207 (accessed [today's date]).

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