Is DCTN1 p.Arg409Gln (c.1226G>A) pathogenic?

DCTN1 p.Arg409Gln (c.1226G>A) is classified Conflicting classifications of pathogenicity in DCTN1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0864); Very rare (popmax 0.00881%, nfe); Associated with Perry syndrome.

What condition is associated with DCTN1 p.Arg409Gln (c.1226G>A)?

DCTN1 p.Arg409Gln (c.1226G>A) is associated with Perry syndrome, amyotrophic lateral sclerosis type 1, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Arg409Gln (c.1226G>A) in the general population?

DCTN1 p.Arg409Gln (c.1226G>A) is very rare (popmax 0.00881%, nfe) (gnomAD).

How is Perry syndrome inherited?

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

What do computational predictors say about DCTN1 p.Arg409Gln (c.1226G>A)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

DCTN1 p.Arg409Gln

c.1226G>A · rs142318791 · VCV844212

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00881%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Perry syndrome

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,940 bp · p 6.9e-06 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00881% European (non-Finnish) · 104/1,180,054 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00731% 118/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00881%	11,347
Admixed American	0.00666%	15,008
South Asian	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0032%	31,256
African / African-American	0.00266%	37,526

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.Arg409Gln
Coding: c.1226G>A
MANE Select: NM_004082
dbSNP: rs142318791
Type: single nucleotide variant
Location: chr2:74370247 (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.Arg409Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
DCTN1 p.Arg409= Likely benign ★ 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

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-arg409gln (accessed [today's date]).

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