Is DHTKD1 p.Phe841= (c.2523C>T) pathogenic?

DHTKD1 p.Phe841= (c.2523C>T) is classified Benign in DHTKD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.59%, afr); Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Phe841= (c.2523C>T)?

DHTKD1 p.Phe841= (c.2523C>T) is associated with 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Phe841= (c.2523C>T) in the general population?

DHTKD1 p.Phe841= (c.2523C>T) is low-frequency (popmax 3.59%, afr) (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.Phe841=

c.2523C>T · rs12769375 · VCV780845

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.59%, afr)

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 0.78	GERP -0.14, phastCons 1
Overall
CADD	6.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.59% African / African-American · 2,675/74,592 alleles

Filtering AF 3.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.43%

Overall 0.185% 2,978/1,606,480 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.59%	28
Remaining individualsnot grpmax-eligible	0.252%	396
Admixed American	0.194%	514
Middle Eastern	0.0663%	1,509
South Asian	0.0067%	14,934
European (non-Finnish)	0.00187%	53,494

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.Phe841=
Coding: c.2523C>T
MANE Select: NM_018706
dbSNP: rs12769375
Type: single nucleotide variant
Location: chr10:12118869 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 841: 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.Phe841Leu 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-phe841 (accessed [today's date]).

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