Is GMPPB p.Ser98fs (c.291_294del) pathogenic?

GMPPB p.Ser98fs (c.291294del) is classified Likely pathogenic in GMPPB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-02). No gnomAD frequency available for this variant; Associated with myopathy caused by variation in GMPPB.

What condition is associated with GMPPB p.Ser98fs (c.291_294del)?

GMPPB p.Ser98fs (c.291_294del) is associated with myopathy caused by variation in GMPPB (ClinVar).

How common is GMPPB p.Ser98fs (c.291_294del) in the general population?

GMPPB p.Ser98fs (c.291_294del) is no gnomAD frequency available for this variant (gnomAD).

GMPPB p.Ser98fs

c.291_294del · rs1175885498 · VCV2500893

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

myopathy caused by variation in GMPPB

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1

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: GMPPB
Protein: p.Ser98fs
Coding: c.291_294del
MANE Select: NM_021971
dbSNP: rs1175885498
Type: Microsatellite
Location: chr3:49723080 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 98: the 'substrate-binding domain' region; a β-strand

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

Disease context

myopathy caused by variation in GMPPB — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GMPPB p.Val343Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
GMPPB p.Thr153fs Pathogenic/Likely pathogenic ★★ same type
GMPPB p.Cys285fs Pathogenic ★ same type
GMPPB p.Tyr337fs Likely pathogenic ★ same type
GMPPB c.951+14CTGGG[3] Uncertain significance ★ same type
GMPPB p.Glu196del Uncertain significance ★ same type
GMPPB c.210+9_210+10del Likely benign ★ same type
GMPPB c.211-13CT[3] Likely benign ★ 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/gmppb-p-ser98fs (accessed [today's date]).

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