Is DHTKD1 p.Pro799fs (c.2396_2397del) pathogenic?

DHTKD1 p.Pro799fs (c.23962397del) is classified Likely pathogenic in DHTKD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-30). Ultra-rare (popmax 0.0167%, mid); Associated with DHTKD1-related disorder.

What condition is associated with DHTKD1 p.Pro799fs (c.2396_2397del)?

DHTKD1 p.Pro799fs (c.2396_2397del) is associated with DHTKD1-related disorder (ClinVar).

How common is DHTKD1 p.Pro799fs (c.2396_2397del) in the general population?

DHTKD1 p.Pro799fs (c.2396_2397del) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

DHTKD1 p.Pro799fs

c.2396_2397del · rs757583515 · VCV1324228

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Conditions

DHTKD1-related disorder

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 14 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,986 alleles

Filtering AF 0.00453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00324%

Overall 0.000696% 11/1,580,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,986
South Asian	0.00916%	10,914
Remaining individualsnot grpmax-eligible	0.00327%	30,626

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.Pro799fs
Coding: c.2396_2397del
MANE Select: NM_018706
dbSNP: rs757583515
Type: Deletion
Location: chr10:12117749 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 799: 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

DHTKD1-related disorder

Similar variants

DHTKD1 p.Val423fs Likely pathogenic ★ same condition
DHTKD1 c.2572+1G>A Likely pathogenic ★★ same condition
DHTKD1 p.Arg410Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Arg712Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Trp687Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Tyr853Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Gln510Ter Likely pathogenic ★ same condition
DHTKD1 p.Gly729Arg Conflicting classifications of pathogenicity ★ ⚠ 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-pro799fs (accessed [today's date]).

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