Is DHTKD1 p.Ser602fs (c.1806_1809del) pathogenic?

DHTKD1 p.Ser602fs (c.18061809del) is classified Pathogenic in DHTKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-17). Ultra-rare (popmax 0.0121%, sas); Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Ser602fs (c.1806_1809del)?

DHTKD1 p.Ser602fs (c.1806_1809del) is associated with 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Ser602fs (c.1806_1809del) in the general population?

DHTKD1 p.Ser602fs (c.1806_1809del) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

How is 2-aminoadipic 2-oxoadipic aciduria inherited?

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

DHTKD1 p.Ser602fs

c.1806_1809del · rs761024388 · VCV2718150

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

2-aminoadipic 2-oxoadipic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 0.72, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,082 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000752% 11/1,461,882 alleles · ultra-rare

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: DHTKD1
Protein: p.Ser602fs
Coding: c.1806_1809del
MANE Select: NM_018706
dbSNP: rs761024388
Type: Microsatellite
Location: chr10:12101087 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 602: a UniProt-annotated variant site (in aakad)

Full DHTKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

2-aminoadipic 2-oxoadipic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 2-aminoadipic 2-oxoadipic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

DHTKD1 p.Thr461fs Pathogenic ★★ same condition
DHTKD1 p.Glu821fs Pathogenic ★ same condition
DHTKD1 c.2659-3_2659-2del Conflicting classifications of pathogenicity ★ same condition
DHTKD1 p.Ile219del Uncertain significance ★ same condition
DHTKD1 p.Ile425del Uncertain significance ★ same condition
DHTKD1 p.Ter920= Uncertain significance ★ same condition
DHTKD1 p.Thr787del Uncertain significance ★ same condition
DHTKD1 c.1359-13_1359-12del Likely 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/dhtkd1-p-ser602fs (accessed [today's date]).

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