Is GNE p.Arg306Gln (c.917G>A) pathogenic?

GNE p.Arg306Gln (c.917G>A) is classified Likely pathogenic in GNE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-17). AlphaMissense: likely pathogenic (0.9642); Very rare (popmax 0.00223%, eas); Associated with sialuria.

What condition is associated with GNE p.Arg306Gln (c.917G>A)?

GNE p.Arg306Gln (c.917G>A) is associated with sialuria, GNE myopathy, thrombocytopenia 12 with or without myopathy (ClinVar).

How common is GNE p.Arg306Gln (c.917G>A) in the general population?

GNE p.Arg306Gln (c.917G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Sialuria inherited?

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

What do computational predictors say about GNE p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely pathogenic (score 0.9642) — an in-silico prediction, not a clinical call.

GNE p.Arg306Gln

c.917G>A · rs1455785164 · VCV498574

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sialuria

Computational evidence

Protein change
AlphaMissense	0.9642	likely pathogenic ✓ concordant with ClinVar
REVEL	0.872	moderately pathogenic-leaning
SaProt	LLR -10.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 1.8e-23 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 0.000186% 3/1,614,204 alleles · very rare exomes 3/1,461,886 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
Finnishnot grpmax-eligible	0.00156%	64,040
European (non-Finnish)	8.47e-05%	1,180,026

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_005476
dbSNP: rs1455785164
Type: single nucleotide variant
Location: chr9:36233985 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 5 PDB
Residue 306: an α-helix; a UniProt-annotated variant site (in nm)

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 thrombocytopenia 12 with or without myopathy

For Sialuria (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

GNE p.Arg306Ter Pathogenic ★★ same residue
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

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-arg306gln (accessed [today's date]).

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