Is GMPPB p.Ser57Phe (c.170_171delinsTC) pathogenic?

GMPPB p.Ser57Phe (c.170171delinsTC) is classified Uncertain significance in GMPPB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2T.

How common is GMPPB p.Ser57Phe (c.170_171delinsTC) in the general population?

GMPPB p.Ser57Phe (c.170_171delinsTC) is absent from gnomAD (gnomAD).

How is GMPPB-related limb-girdle muscular dystrophy R19 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GMPPB p.Ser57Phe

Q: What condition is associated with GMPPB p.Ser57Phe (c.170_171delinsTC)?

GMPPB p.Ser57Phe (c.170_171delinsTC) is associated with autosomal recessive limb-girdle muscular dystrophy type 2T, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 (ClinVar).

c.170_171delinsTC · rs2544757385 · VCV1715757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2T

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -4.8
Regional constraint	o/e 0.90	unconstrained · MANE · 1,971 bp · p 0.021 · regional, not allelic

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.Ser57Phe
Coding: c.170_171delinsTC
MANE Select: NM_021971
dbSNP: rs2544757385
Type: Indel
Location: chr3:49723431 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 57: the 'substrate-binding domain' region; an α-helix

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2T — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14

For GMPPB-related limb-girdle muscular dystrophy R19 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

GMPPB p.Ser57= Likely benign ★ same residue
GMPPB p.Arg243fs Pathogenic/Likely pathogenic ★★ same condition
GMPPB p.Asp114His Uncertain significance ★ same condition
GMPPB p.Glu130Arg Uncertain significance ★ same condition
GMPPB c.129+1G>T Likely pathogenic ★★ same condition
GMPPB c.402+1G>A Pathogenic/Likely pathogenic ★★ same condition
GMPPB c.640+1G>A Pathogenic/Likely pathogenic ★★ same condition
GMPPB c.640+1G>C 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/gmppb-p-ser57phe (accessed [today's date]).

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