Is DCTN1 p.Pro150= (c.450C>T) pathogenic?

DCTN1 p.Pro150= (c.450C>T) is classified Likely benign in DCTN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-20). Ultra-rare (popmax 0.0312%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCTN1 p.Pro150= (c.450C>T)?

DCTN1 p.Pro150= (c.450C>T) is associated with Inborn genetic diseases, amyotrophic lateral sclerosis type 1, Perry syndrome (ClinVar).

How common is DCTN1 p.Pro150= (c.450C>T) in the general population?

DCTN1 p.Pro150= (c.450C>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

DCTN1 p.Pro150=

c.450C>T · rs762745227 · VCV536170

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Conditions

Inborn genetic diseases

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 5.8	GERP -2.4, phastCons 1
Overall
CADD	10.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,886 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00157% 23/1,461,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
Admixed American	0.015%	6,668

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.Pro150=
Coding: c.450C>T
MANE Select: NM_004082
dbSNP: rs762745227
Type: single nucleotide variant
Location: chr2:74372931 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 13 PDB
Residue 150: the 'disordered' region

Full DCTN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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-pro150 (accessed [today's date]).

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