Is GNE p.Arg720= (c.2160G>A) pathogenic?

GNE p.Arg720= (c.2160G>A) is classified Likely benign in GNE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). Absent from gnomAD v4.1; Associated with sialuria.

What condition is associated with GNE p.Arg720= (c.2160G>A)?

GNE p.Arg720= (c.2160G>A) is associated with sialuria, GNE myopathy (ClinVar).

How common is GNE p.Arg720= (c.2160G>A) in the general population?

GNE p.Arg720= (c.2160G>A) is absent from gnomAD v4.1 (gnomAD).

How is Sialuria inherited?

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

GNE p.Arg720=

c.2160G>A · rs2489580225 · VCV2154858

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

sialuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.61	GERP 1.7, phastCons 0.93
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GNE
Protein: p.Arg720=
Coding: c.2160G>A
MANE Select: NM_005476
dbSNP: rs2489580225
Type: single nucleotide variant
Location: chr9:36217374 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 5 PDB
Residue 720: the 'n-acetylmannosamine kinase' region; a UniProt-annotated variant site (in thc12; likely pathogenic)

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

Disease context

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

Also linked: GNE myopathy

For Sialuria (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

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-arg720 (accessed [today's date]).

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