Is KHK p.Ser169= (c.507C>T) pathogenic?

KHK p.Ser169= (c.507C>T) is classified Uncertain significance in KHK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.333%, afr); Associated with essential fructosuria.

What condition is associated with KHK p.Ser169= (c.507C>T)?

KHK p.Ser169= (c.507C>T) is associated with essential fructosuria (ClinVar).

How common is KHK p.Ser169= (c.507C>T) in the general population?

KHK p.Ser169= (c.507C>T) is rare (popmax 0.333%, afr) (gnomAD).

How is Essential fructosuria inherited?

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

KHK p.Ser169=

c.507C>T · rs148222785 · VCV898355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.333%, afr)

Conditions

essential fructosuria

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 -20	GERP -4.7
Overall
CADD	0.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.333% African / African-American · 250/75,052 alleles

Filtering AF 0.299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.286%

Overall 0.0212% 342/1,614,014 alleles · rare exomes 184/1,461,710 · genomes 158/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.333%	300
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0208%	4,808
European (non-Finnish)	0.00407%	24,584
East Asian	0.00223%	44,888
South Asian	0.0011%	91,084

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.Ser169=
Coding: c.507C>T
MANE Select: NM_006488
dbSNP: rs148222785
Type: single nucleotide variant
Location: chr2:27097592 (GRCh38)
Gene constraint: LOEUF 1.362 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.32 · 38 PDB
Residue 169: 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-ser169 (accessed [today's date]).

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