Is DCTN1 p.Asp712= (c.2136T>C) pathogenic?

DCTN1 p.Asp712= (c.2136T>C) is classified Benign/Likely benign in DCTN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-07). Rare (popmax 0.992%, eas); Associated with neuronopathy, distal hereditary motor, type 7B.

What condition is associated with DCTN1 p.Asp712= (c.2136T>C)?

DCTN1 p.Asp712= (c.2136T>C) is associated with neuronopathy, distal hereditary motor, type 7B, amyotrophic lateral sclerosis type 1, Perry syndrome (ClinVar).

How common is DCTN1 p.Asp712= (c.2136T>C) in the general population?

DCTN1 p.Asp712= (c.2136T>C) is rare (popmax 0.992%, eas) (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.Asp712=

c.2136T>C · rs147297927 · VCV337084

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.992%, eas)

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 -0.28	GERP -3.2, phastCons 0.001
Overall
CADD	2.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.992% East Asian · 445/44,880 alleles

Filtering AF 0.915% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.885%

Overall 0.0278% 448/1,614,166 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.992%	101
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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.Asp712=
Coding: c.2136T>C
MANE Select: NM_004082
dbSNP: rs147297927
Type: single nucleotide variant
Location: chr2:74367744 (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 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-asp712 (accessed [today's date]).

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