Is GNE p.Pro16= (c.48T>A) pathogenic?

GNE p.Pro16= (c.48T>A) is classified Likely benign in GNE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). Very rare (popmax 0.00102%, nfe); Associated with sialuria.

What condition is associated with GNE p.Pro16= (c.48T>A)?

GNE p.Pro16= (c.48T>A) is associated with sialuria, GNE myopathy (ClinVar).

How common is GNE p.Pro16= (c.48T>A) in the general population?

GNE p.Pro16= (c.48T>A) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is Sialuria inherited?

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

GNE p.Pro16=

c.48T>A · rs769211820 · VCV1951907

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

sialuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.63, phastCons 1
Overall
CADD	12.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,176,988 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000746% 12/1,609,640 alleles · very rare exomes 12/1,457,464 · genomes 0/152,176 · 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.Pro16=
Coding: c.48T>A
MANE Select: NM_005476 · reported on NM_001128227
dbSNP: rs769211820
Type: single nucleotide variant
Location: chr9:36276897 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 5 PDB
Residue 16: a β-strand

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 p.Thr16Ala Uncertain significance ★ ⚠ 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-pro16 (accessed [today's date]).

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