Is KHK p.Gln5= (c.15G>A) pathogenic?

KHK p.Gln5= (c.15G>A) is classified Uncertain significance in KHK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with essential fructosuria.

What condition is associated with KHK p.Gln5= (c.15G>A)?

KHK p.Gln5= (c.15G>A) is associated with essential fructosuria (ClinVar).

How common is KHK p.Gln5= (c.15G>A) in the general population?

KHK p.Gln5= (c.15G>A) is absent from gnomAD v4.1 (gnomAD).

How is Essential fructosuria inherited?

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

KHK p.Gln5=

c.15G>A · rs1669712582 · VCV895295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

essential fructosuria

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 7.4	GERP 1.2, phastCons 1
Overall
CADD	13.04	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: KHK
Protein: p.Gln5=
Coding: c.15G>A
MANE Select: NM_006488
dbSNP: rs1669712582
Type: single nucleotide variant
Location: chr2:27087274 (GRCh38)
Gene constraint: LOEUF 1.362 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.32 · 38 PDB
Residue 5: a β-strand

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

Disease context

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

For Essential fructosuria (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

KHK p.Ala155Thr Uncertain significance ★★ ⚠ same condition
KHK p.Asn157Thr Uncertain significance ★★ ⚠ same condition
KHK p.Ser273Asn Uncertain significance ★★ ⚠ same condition
KHK p.Thr158Asn Uncertain significance ★★ ⚠ same condition
KHK c.210-328A>G Benign ★★ same condition
KHK c.-245G>A Benign ★★ same condition
KHK c.-324C>T Benign ★★ same condition
KHK c.-469A>C Benign ★★ 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/khk-p-gln5 (accessed [today's date]).

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