Is DHTKD1 p.Phe20fs (c.58_59del) pathogenic?

DHTKD1 p.Phe20fs (c.5859del) is classified Pathogenic in DHTKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Phe20fs (c.58_59del)?

DHTKD1 p.Phe20fs (c.58_59del) is associated with 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How is 2-aminoadipic 2-oxoadipic aciduria inherited?

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

DHTKD1 p.Phe20fs

c.58_59del · VCV4704454

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 1 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP 1.2

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

Variant & gene context

Gene: DHTKD1
Protein: p.Phe20fs
Coding: c.58_59del
MANE Select: NM_018706
Type: Deletion
Location: chr10:12069091 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 20: a UniProt-annotated variant site (in)

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.Phe20Leu Benign ★★ same residue
DHTKD1 p.Phe20= Benign ★ same residue
DHTKD1 p.Glu250fs Pathogenic ★★ same condition
DHTKD1 p.Gly470fs Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 c.1742_1756+29del Likely pathogenic ★ same condition
DHTKD1 c.2048-8_2050del Likely pathogenic ★ same condition
DHTKD1 p.Ala783fs Pathogenic ★ same condition
DHTKD1 p.Glu111fs 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/dhtkd1-p-phe20fs (accessed [today's date]).

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