Is DHTKD1 p.Arg892Leu (c.2675G>T) pathogenic?

DHTKD1 p.Arg892Leu (c.2675G>T) is classified Uncertain significance in DHTKD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-12). AlphaMissense: likely pathogenic (0.8142); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with DHTKD1 p.Arg892Leu (c.2675G>T)?

DHTKD1 p.Arg892Leu (c.2675G>T) is associated with Inborn genetic diseases, 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Arg892Leu (c.2675G>T) in the general population?

DHTKD1 p.Arg892Leu (c.2675G>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DHTKD1 p.Arg892Leu (c.2675G>T)?

AlphaMissense predicts likely pathogenic (score 0.8142) — an in-silico prediction, not a clinical call.

DHTKD1 p.Arg892Leu

c.2675G>T · rs574614585 · VCV1396655

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8142 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8142	likely pathogenic
REVEL	0.576	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 52 kb · p 0.072 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,052 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00279% 45/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,026
Admixed American	0.0217%	4,616
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.00549%	18,216
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,517
European (non-Finnish)	0.00127%	78,663

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.Arg892Leu
Coding: c.2675G>T
MANE Select: NM_018706
dbSNP: rs574614585
Type: single nucleotide variant
Location: chr10:12120803 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 892: a UniProt-annotated variant site (in aakad); a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 2-aminoadipic 2-oxoadipic aciduria

Similar variants

DHTKD1 p.Arg892Gln 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-arg892leu (accessed [today's date]).

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