Is KHK p.Val16= (c.48C>T) pathogenic?

KHK p.Val16= (c.48C>T) is classified Uncertain significance in KHK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.0476%, nfe); Associated with essential fructosuria.

What condition is associated with KHK p.Val16= (c.48C>T)?

KHK p.Val16= (c.48C>T) is associated with essential fructosuria (ClinVar).

How common is KHK p.Val16= (c.48C>T) in the general population?

KHK p.Val16= (c.48C>T) is ultra-rare (popmax 0.0476%, nfe) (gnomAD).

How is Essential fructosuria inherited?

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

KHK p.Val16=

c.48C>T · rs200769127 · VCV896715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0476%, nfe)

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 2.2	GERP 1.2, phastCons 1
Overall
CADD	14.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0476% European (non-Finnish) · 559/1,173,608 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0431%

Overall 0.037% 593/1,601,186 alleles · ultra-rare exomes 567/1,448,988 · genomes 26/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0476%	2,099
Remaining individualsnot grpmax-eligible	0.0258%	3,873
Finnishnot grpmax-eligible	0.0143%	7,008
African / African-American	0.00803%	12,456
Admixed American	0.00513%	19,485

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: KHK
Protein: p.Val16=
Coding: c.48C>T
MANE Select: NM_006488
dbSNP: rs200769127
Type: single nucleotide variant
Location: chr2:27087307 (GRCh38)
Gene constraint: LOEUF 1.362 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.32 · 38 PDB
Residue 16: 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-val16 (accessed [today's date]).

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