Is DHTKD1 p.Leu914= (c.2742C>T) pathogenic?

DHTKD1 p.Leu914= (c.2742C>T) is classified Benign/Likely benign in DHTKD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0825%, mid); Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Leu914= (c.2742C>T)?

DHTKD1 p.Leu914= (c.2742C>T) is associated with 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Leu914= (c.2742C>T) in the general population?

DHTKD1 p.Leu914= (c.2742C>T) is ultra-rare (popmax 0.0825%, mid) (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.Leu914=

c.2742C>T · rs201680688 · VCV770761

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Conditions

2-aminoadipic 2-oxoadipic aciduria

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 -0.086	GERP 0.84
Overall
CADD	5.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.027% 435/1,613,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.571%	175
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.06%	1,666
Remaining individualsnot grpmax-eligible	0.056%	1,785
African / African-American	0.032%	3,122
European (non-Finnish)	0.0137%	7,283
East Asian	0.00223%	44,880
South Asian	0.0022%	45,541
Finnishnot grpmax-eligible	0.00156%	63,994

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.Leu914=
Coding: c.2742C>T
MANE Select: NM_018706
dbSNP: rs201680688
Type: single nucleotide variant
Location: chr10:12120870 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 914: 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 p.Leu914Val Uncertain significance ★★ ⚠ same residue
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

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-leu914 (accessed [today's date]).

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