Is GMPPB p.Cys306= (c.918C>T) pathogenic?

GMPPB p.Cys306= (c.918C>T) is classified Likely benign in GMPPB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-14). Very rare (popmax 0.000171%, nfe); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14.

What condition is associated with GMPPB p.Cys306= (c.918C>T)?

GMPPB p.Cys306= (c.918C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14, autosomal recessive limb-girdle muscular dystrophy type 2T (ClinVar).

How common is GMPPB p.Cys306= (c.918C>T) in the general population?

GMPPB p.Cys306= (c.918C>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

GMPPB p.Cys306=

c.918C>T · rs1186936513 · VCV743221

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.8, phastCons 1
Overall
CADD	7.721	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,166,786 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000189% 3/1,590,550 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00164%	61,050
European (non-Finnish)grpmax	0.000171%	583,393

Remaining individuals 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: GMPPB
Protein: p.Cys306=
Coding: c.918C>T
MANE Select: NM_021971
dbSNP: rs1186936513
Type: single nucleotide variant
Location: chr3:49721998 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 306: the 'hexapeptide repeat domain' region

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

Disease context

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 autosomal recessive limb-girdle muscular dystrophy type 2T

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

GMPPB p.Cys306Trp Uncertain significance ★ ⚠ 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-cys306 (accessed [today's date]).

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