Is DHTKD1 p.Asp565His (c.1693G>C) pathogenic?

DHTKD1 p.Asp565His (c.1693G>C) is classified Uncertain significance in DHTKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.00174%, amr); Associated with Inborn genetic diseases.

What condition is associated with DHTKD1 p.Asp565His (c.1693G>C)?

DHTKD1 p.Asp565His (c.1693G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DHTKD1 p.Asp565His (c.1693G>C) in the general population?

DHTKD1 p.Asp565His (c.1693G>C) is very rare (popmax 0.00174%, amr) (gnomAD).

What do computational predictors say about DHTKD1 p.Asp565His (c.1693G>C)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

DHTKD1 p.Asp565His

c.1693G>C · VCV4617310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.287	benign-leaning
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.19, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 52 kb · p 0.072 · regional, not allelic
Overall
CADD	19.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% Admixed American · 1/57,546 alleles

Overall 6.92e-05% 1/1,445,412 alleles · very rare

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.Asp565His
Coding: c.1693G>C
MANE Select: NM_018706
Type: single nucleotide variant
Location: chr10:12100199 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 565: 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

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

Similar variants

DHTKD1 p.Asp565Gly Uncertain significance ★ ⚠ same residue
DHTKD1 p.Asp565= Benign/Likely benign ★★ same residue
DHTKD1 p.Trp861Ter Pathogenic ★★ same condition
DHTKD1 c.1159+5G>A Uncertain significance ★★ same condition
DHTKD1 p.Ala113Pro Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala275Val Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala297Val Uncertain significance ★★ ⚠ same condition
DHTKD1 p.Ala723Val Uncertain significance ★★ ⚠ 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-asp565his (accessed [today's date]).

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