Is GMPPB p.Arg313= (c.939C>T) pathogenic?

GMPPB p.Arg313= (c.939C>T) is classified Likely benign in GMPPB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-29). Rare (popmax 0.103%, eas); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14.

What condition is associated with GMPPB p.Arg313= (c.939C>T)?

GMPPB p.Arg313= (c.939C>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.Arg313= (c.939C>T) in the general population?

GMPPB p.Arg313= (c.939C>T) is rare (popmax 0.103%, eas) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

GMPPB p.Arg313=

c.939C>T · rs147714661 · VCV715300

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.103%, eas)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.3	GERP -4.8
Overall
CADD	2.179	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% East Asian · 21/20,370 alleles

Filtering AF 0.0821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0747%

Overall 0.00956% 116/1,213,472 alleles · rare exomes 86/1,072,942 · genomes 30/140,530 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.103%	970
African / African-American	0.102%	979
Remaining individualsnot grpmax-eligible	0.0145%	6,902
South Asian	0.00474%	21,108
European (non-Finnish)	0.00225%	44,378
Admixed American	0.00194%	51,496

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.Arg313=
Coding: c.939C>T
MANE Select: NM_021971
dbSNP: rs147714661
Type: single nucleotide variant
Location: chr3:49721977 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.33 · 3 PDB
Residue 313: 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.Arg313Cys Uncertain significance ★★ ⚠ same residue
GMPPB p.Arg313His Uncertain significance ★★ ⚠ same residue
GMPPB p.Arg313Leu 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

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-arg313 (accessed [today's date]).

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