Is DCTN1 p.Ala355= (c.1065A>T) pathogenic?

DCTN1 p.Ala355= (c.1065A>T) is classified Conflicting classifications of pathogenicity in DCTN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-07-11). Absent from gnomAD v4.1; Associated with neuronopathy, distal hereditary motor, type 7B.

What condition is associated with DCTN1 p.Ala355= (c.1065A>T)?

DCTN1 p.Ala355= (c.1065A>T) is associated with neuronopathy, distal hereditary motor, type 7B, Perry syndrome (ClinVar).

How common is DCTN1 p.Ala355= (c.1065A>T) in the general population?

DCTN1 p.Ala355= (c.1065A>T) is absent from gnomAD v4.1 (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.Ala355=

c.1065A>T · rs886056333 · VCV337091

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -14	GERP -4.3
Overall
CADD	0.311	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCTN1
Protein: p.Ala355=
Coding: c.1065A>T
MANE Select: NM_004082
dbSNP: rs886056333
Type: single nucleotide variant
Location: chr2:74370528 (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: Perry syndrome

For Distal hereditary motor neuropathy type 7 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

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
DCTN1 c.33+3A>G 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-ala355 (accessed [today's date]).

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