Is GNE p.Pro314= (c.942T>C) pathogenic?

GNE p.Pro314= (c.942T>C) is classified Likely benign in GNE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). Very rare (popmax 8.47e-05%, nfe); Associated with GNE myopathy.

What condition is associated with GNE p.Pro314= (c.942T>C)?

GNE p.Pro314= (c.942T>C) is associated with GNE myopathy, sialuria (ClinVar).

How common is GNE p.Pro314= (c.942T>C) in the general population?

GNE p.Pro314= (c.942T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is GNE myopathy inherited?

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

GNE p.Pro314=

c.942T>C · rs2133068079 · VCV1654193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

GNE myopathy

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 0.17	GERP -1.9, phastCons 0.17
Overall
CADD	8.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,614,180 alleles · very rare exomes 1/1,461,856 · genomes 0/152,324 · joint denominator

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: GNE
Protein: p.Pro314=
Coding: c.942T>C
MANE Select: NM_005476
dbSNP: rs2133068079
Type: single nucleotide variant
Location: chr9:36233960 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 5 PDB

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

Disease context

GNE myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sialuria

For GNE myopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

GNE c.1816+2T>C Pathogenic/Likely pathogenic ★★ same condition
GNE c.1816+5G>A Pathogenic ★★ same condition
GNE c.617-1G>A Likely pathogenic ★★ same condition
GNE c.617-2A>G Pathogenic/Likely pathogenic ★★ same condition
GNE c.982+2T>A Likely pathogenic ★★ same condition
GNE p.Ala524Val Pathogenic/Likely pathogenic ★★ same condition
GNE p.Ala630Thr Pathogenic/Likely pathogenic ★★ same condition
GNE p.Ala631Thr 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/gne-p-pro314 (accessed [today's date]).

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