Is GMPPB p.Pro32Ser (c.94C>T) pathogenic?

GMPPB p.Pro32Ser (c.94C>T) is classified Conflicting classifications of pathogenicity in GMPPB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-03-07). AlphaMissense: ambiguous (0.4859); Absent from gnomAD v4.1; Associated with muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14.

What condition is associated with GMPPB p.Pro32Ser (c.94C>T)?

GMPPB p.Pro32Ser (c.94C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, autosomal recessive limb-girdle muscular dystrophy type 2T (ClinVar).

How common is GMPPB p.Pro32Ser (c.94C>T) in the general population?

GMPPB p.Pro32Ser (c.94C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GMPPB p.Pro32Ser (c.94C>T)?

AlphaMissense predicts ambiguous (score 0.4859) — an in-silico prediction, not a clinical call.

GMPPB p.Pro32Ser

c.94C>T · rs1575297292 · VCV654897

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4859 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,584,372)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14

Computational evidence

Protein change
AlphaMissense	0.4859	ambiguous
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -10.84	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,971 bp · p 0.021 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,584,372). 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.Pro32Ser
Coding: c.94C>T
MANE Select: NM_021971
dbSNP: rs1575297292
Type: single nucleotide variant
Location: chr3:49723633 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 32: the 'substrate-binding domain' region; a UniProt-annotated variant site (in mddgb14; causes protein aggregation; reduces catalytic activity; fails to rescue phenotype when expressed in a zebrafish disease model); a UniProt-annotated variant site (in mddgc14); a β-strand

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

Disease context

muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 autosomal recessive limb-girdle muscular dystrophy type 2T

Similar variants

GMPPB p.Pro32Leu Pathogenic ★★ same residue
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
GMPPB p.Arg185Cys Pathogenic/Likely pathogenic ★★ same condition
GMPPB p.Arg287Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
GMPPB p.Arg287Trp 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-pro32ser (accessed [today's date]).

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