Is DCTN1 p.Pro140= (c.420G>A) pathogenic?

DCTN1 p.Pro140= (c.420G>A) is classified Likely benign in DCTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). Ultra-rare (popmax 0.02%, amr); Associated with Perry syndrome.

What condition is associated with DCTN1 p.Pro140= (c.420G>A)?

DCTN1 p.Pro140= (c.420G>A) is associated with Perry syndrome, amyotrophic lateral sclerosis type 1, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Pro140= (c.420G>A) in the general population?

DCTN1 p.Pro140= (c.420G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

How is Perry syndrome inherited?

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

DCTN1 p.Pro140=

c.420G>A · rs375040197 · VCV703808

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

Perry syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Overall
CADD	16.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,930 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00899%

Overall 0.00273% 44/1,612,688 alleles · ultra-rare exomes 36/1,460,800 · genomes 8/151,888 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,994
Middle Eastern	0.0165%	6,078
African / African-American	0.00535%	18,688
Remaining individualsnot grpmax-eligible	0.00481%	20,799
European (non-Finnish)	0.00203%	49,143

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.Pro140=
Coding: c.420G>A
MANE Select: NM_004082
dbSNP: rs375040197
Type: single nucleotide variant
Location: chr2:74374335 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 13 PDB
Residue 140: the 'disordered' region

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.Pro140Gln Uncertain significance ★ ⚠ same residue
DCTN1 p.Pro140Leu Uncertain significance ★ ⚠ same residue
DCTN1 p.Pro140Thr 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

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-pro140 (accessed [today's date]).

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