Is GNE p.Phe437= (c.1311C>T) pathogenic?

GNE p.Phe437= (c.1311C>T) is classified Likely benign in GNE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). Very rare (popmax 0.000425%, nfe); Associated with sialuria.

What condition is associated with GNE p.Phe437= (c.1311C>T)?

GNE p.Phe437= (c.1311C>T) is associated with sialuria, GNE myopathy (ClinVar).

How common is GNE p.Phe437= (c.1311C>T) in the general population?

GNE p.Phe437= (c.1311C>T) is very rare (popmax 0.000425%, nfe) (gnomAD).

How is Sialuria inherited?

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

GNE p.Phe437=

c.1311C>T · rs1554659051 · VCV460452

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

sialuria

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 6.6	GERP 0.72, phastCons 1
Overall
CADD	10.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,176,942 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000311% 5/1,610,222 alleles · very rare exomes 5/1,458,114 · genomes 0/152,108 · 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.Phe437=
Coding: c.1311C>T
MANE Select: NM_005476
dbSNP: rs1554659051
Type: single nucleotide variant
Location: chr9:36223473 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 5 PDB
Residue 437: a β-strand; 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 p.Phe437Ser 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-phe437 (accessed [today's date]).

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