Is DCTN1 p.Asp333= (c.999C>T) pathogenic?

DCTN1 p.Asp333= (c.999C>T) is classified Benign in DCTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). Ultra-rare (popmax 0.0922%, sas); Associated with neuronopathy, distal hereditary motor, type 7B.

What condition is associated with DCTN1 p.Asp333= (c.999C>T)?

DCTN1 p.Asp333= (c.999C>T) is associated with neuronopathy, distal hereditary motor, type 7B, amyotrophic lateral sclerosis type 1, Perry syndrome (ClinVar).

How common is DCTN1 p.Asp333= (c.999C>T) in the general population?

DCTN1 p.Asp333= (c.999C>T) is ultra-rare (popmax 0.0922%, sas) (gnomAD).

How is Distal hereditary motor neuropathy type 7 inherited?

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

DCTN1 p.Asp333=

c.999C>T · rs200952455 · VCV771985

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, sas)

Conditions

neuronopathy, distal hereditary motor, type 7B

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 -11	GERP -4.6
Overall
CADD	0.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0922% South Asian · 84/91,078 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00861% 139/1,614,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0922%	1,084
Admixed American	0.0217%	4,617
African / African-American	0.00933%	10,718
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.0028%	35,759

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: DCTN1
Protein: p.Asp333=
Coding: c.999C>T
MANE Select: NM_004082
dbSNP: rs200952455
Type: single nucleotide variant
Location: chr2:74370670 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 13 PDB

Full DCTN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronopathy, distal hereditary motor, type 7B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 1 Perry syndrome

For Distal hereditary motor neuropathy type 7 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

DCTN1 p.Asp333Glu Uncertain significance ★ ⚠ same residue
DCTN1 c.279+1G>T Pathogenic/Likely pathogenic ★★ same condition
DCTN1 p.Gln93His Pathogenic/Likely pathogenic ★★ same condition
DCTN1 p.Gly71Glu Pathogenic ★★ same condition
DCTN1 p.Tyr78His Likely pathogenic ★★ same condition
DCTN1 c.1128-3C>G Uncertain significance ★★ same condition
DCTN1 c.1288-10C>G Uncertain significance ★★ same condition
DCTN1 c.2185-3C>T 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/dctn1-p-asp333 (accessed [today's date]).

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