Is DCX p.Thr222= (c.666C>T) pathogenic?

DCX p.Thr222= (c.666C>T) is classified Benign in DCX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-14). Rare (popmax 0.439%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCX p.Thr222= (c.666C>T)?

DCX p.Thr222= (c.666C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCX p.Thr222= (c.666C>T) in the general population?

DCX p.Thr222= (c.666C>T) is rare (popmax 0.439%, eas) (gnomAD).

DCX p.Thr222=

c.666C>T · rs143501582 · VCV715116

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.439%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4.2
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.439% East Asian · 148/33,728 alleles

Filtering AF 0.381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.359%

Overall 0.016% 193/1,209,321 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.439%	228
African / African-American	0.0578%	1,730
Remaining individualsnot grpmax-eligible	0.0063%	15,865
South Asian	0.00176%	56,723
European (non-Finnish)	0.000894%	111,854

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: DCX
Protein: p.Thr222=
Coding: c.666C>T
MANE Select: NM_001195553
dbSNP: rs143501582
Type: single nucleotide variant
Location: chrX:111401029 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 222: the doublecortin 2 domain; a UniProt-annotated variant site (in sbhx)

Full DCX 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

DCX p.Thr222Ile Likely pathogenic ★ same residue
DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg39Ter Pathogenic ★★ same condition
DCX p.Ala295Thr Uncertain significance ★★ ⚠ same condition
DCX p.Cys35Arg Uncertain significance ★★ ⚠ same condition
DCX p.Ile107Thr Uncertain significance ★★ ⚠ same condition
DCX c.706-4A>G Benign/Likely benign ★★ same condition
DCX p.Ala286Ser Benign/Likely benign ★★ 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/dcx-p-thr222 (accessed [today's date]).

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