Is GNE p.Pro27= (c.81G>A) pathogenic?

GNE p.Pro27= (c.81G>A) is classified Likely benign in GNE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-02). Very rare (popmax 0.00223%, eas); Associated with GNE myopathy.

What condition is associated with GNE p.Pro27= (c.81G>A)?

GNE p.Pro27= (c.81G>A) is associated with GNE myopathy, sialuria (ClinVar).

How common is GNE p.Pro27= (c.81G>A) in the general population?

GNE p.Pro27= (c.81G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is GNE myopathy inherited?

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

GNE p.Pro27=

c.81G>A · rs768397785 · VCV1535055

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

GNE myopathy

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 -12	GERP -3.4
Overall
CADD	1.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 0.00031% 5/1,614,090 alleles · very rare exomes 5/1,461,826 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asiangrpmax	0.00223%	44,886
South Asian	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,179,979

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: GNE
Protein: p.Pro27=
Coding: c.81G>A
MANE Select: NM_005476
dbSNP: rs768397785
Type: single nucleotide variant
Location: chr9:36249275 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 5 PDB
Residue 27: 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

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 p.Pro27Leu Pathogenic/Likely pathogenic ★★ same residue
GNE p.Arg27Gln Uncertain significance ★ same residue
GNE p.Arg27Ter Conflicting classifications of pathogenicity ★ 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

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-pro27 (accessed [today's date]).

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