Is DHTKD1 p.Ile693= (c.2079C>T) pathogenic?

DHTKD1 p.Ile693= (c.2079C>T) is classified Benign in DHTKD1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 98%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Charcot-Marie-Tooth disease axonal type 2Q.

What condition is associated with DHTKD1 p.Ile693= (c.2079C>T)?

DHTKD1 p.Ile693= (c.2079C>T) is associated with Charcot-Marie-Tooth disease axonal type 2Q, 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

DHTKD1 p.Ile693=

Q: How common is DHTKD1 p.Ile693= (c.2079C>T) in the general population?

DHTKD1 p.Ile693= (c.2079C>T) is common (popmax 98%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2Q inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2079C>T · rs1722462 · VCV1170355

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 98%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Charcot-Marie-Tooth disease axonal type 2Q

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 -6	GERP -3.9
Overall
CADD	0.115	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98% East Asian · 43,984/44,864 alleles

Filtering AF 97.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 97%

Overall 89.4% 1,441,883/1,613,176 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	98%	1
Amishnot grpmax-eligible	97.6%	1
Finnishnot grpmax-eligible	93%	1
Admixed American	92.7%	1
Middle Eastern	91.7%	1
South Asian	91.2%	1
Ashkenazi Jewishnot grpmax-eligible	91.1%	1
European (non-Finnish)	89.1%	1
Remaining individualsnot grpmax-eligible	89%	1
African / African-American	80.7%	1

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.Ile693=
Coding: c.2079C>T
MANE Select: NM_018706
dbSNP: rs1722462
Type: single nucleotide variant
Location: chr10:12107940 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 693: a UniProt-annotated variant site (in aakad)

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

Disease context

Charcot-Marie-Tooth disease axonal type 2Q — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 2-aminoadipic 2-oxoadipic aciduria

For Autosomal dominant Charcot-Marie-Tooth disease type 2Q (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

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
DHTKD1 p.Arg712Ter 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-ile693 (accessed [today's date]).

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