Is DHTKD1 p.Gln718= (c.2154G>A) pathogenic?

DHTKD1 p.Gln718= (c.2154G>A) is classified Uncertain significance in DHTKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-17). Very rare (popmax 8.5e-05%, nfe); Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Gln718= (c.2154G>A)?

DHTKD1 p.Gln718= (c.2154G>A) is associated with 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Gln718= (c.2154G>A) in the general population?

DHTKD1 p.Gln718= (c.2154G>A) is very rare (popmax 8.5e-05%, nfe) (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.Gln718=

c.2154G>A · rs747366922 · VCV2024974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

2-aminoadipic 2-oxoadipic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.44	donor loss · deltas
Pangolin	Δ0.66	loss · gain 0.14 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 0.96, phastCons 1
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,154 alleles

Overall 0.000249% 4/1,609,610 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,855
European (non-Finnish)grpmax	8.5e-05%	1,176,154

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln718=
Coding: c.2154G>A
MANE Select: NM_018706
dbSNP: rs747366922
Type: single nucleotide variant
Location: chr10:12108015 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 718: a UniProt-annotated variant site (in aakad); an α-helix

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 c.1671+1G>A Likely pathogenic ★★ same condition
DHTKD1 c.1897-1G>A Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 c.2320-2A>T Likely pathogenic ★★ same condition
DHTKD1 c.2572+1G>A Likely pathogenic ★★ same condition
DHTKD1 p.Arg163Ter Pathogenic ★★ same condition
DHTKD1 p.Arg410Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Arg455Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Arg712Ter Pathogenic/Likely 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-gln718 (accessed [today's date]).

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