Is DCTN1 p.Arg643Ter (c.1927C>T) pathogenic?

DCTN1 p.Arg643Ter (c.1927C>T) is classified Uncertain significance in DCTN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-27). Very rare (popmax 0.00133%, afr); Associated with Perry syndrome.

What condition is associated with DCTN1 p.Arg643Ter (c.1927C>T)?

DCTN1 p.Arg643Ter (c.1927C>T) is associated with Perry syndrome, amyotrophic lateral sclerosis type 1, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Arg643Ter (c.1927C>T) in the general population?

DCTN1 p.Arg643Ter (c.1927C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Perry syndrome inherited?

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

DCTN1 p.Arg643Ter

c.1927C>T · rs866457869 · VCV1677992

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Perry syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 17 of 32
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.4, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,026 alleles

Overall 0.000137% 2/1,460,848 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,026
European (non-Finnish)	8.48e-05%	1,179,558

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.Arg643Ter
Coding: c.1927C>T
MANE Select: NM_004082
dbSNP: rs866457869
Type: single nucleotide variant
Location: chr2:74368059 (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

Perry syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 1 neuronopathy, distal hereditary motor, type 7B

For Perry syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

DCTN1 p.Arg643Gln 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-arg643ter (accessed [today's date]).

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