Is MPIG6B p.Ser116fs (c.346_347del) pathogenic?

MPIG6B p.Ser116fs (c.346347del) is classified Likely pathogenic in MPIG6B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). No gnomAD frequency available for this variant; Associated with thrombocytopenia, anemia, and myelofibrosis.

What condition is associated with MPIG6B p.Ser116fs (c.346_347del)?

MPIG6B p.Ser116fs (c.346_347del) is associated with thrombocytopenia, anemia, and myelofibrosis (ClinVar).

How common is MPIG6B p.Ser116fs (c.346_347del) in the general population?

MPIG6B p.Ser116fs (c.346_347del) is no gnomAD frequency available for this variant (gnomAD).

MPIG6B p.Ser116fs

c.346_347del · rs2537274178 · VCV3065571

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

thrombocytopenia, anemia, and myelofibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.5	GERP -3.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MPIG6B
Protein: p.Ser116fs
Coding: c.346_347del
MANE Select: NM_138272
dbSNP: rs2537274178
Type: Microsatellite
Location: chr6:31723920 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 1 PDB
Residue 116: 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.Ala52fs Pathogenic/Likely pathogenic ★★ same condition
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

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-ser116fs (accessed [today's date]).

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