Is DCTN1 p.Ser874= (c.2622C>T) pathogenic?

DCTN1 p.Ser874= (c.2622C>T) is classified Uncertain significance in DCTN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-08). Very rare (popmax 0.00669%, eas); Associated with DCTN1-related disorder.

What condition is associated with DCTN1 p.Ser874= (c.2622C>T)?

DCTN1 p.Ser874= (c.2622C>T) is associated with DCTN1-related disorder, amyotrophic lateral sclerosis type 1, Perry syndrome (ClinVar).

How common is DCTN1 p.Ser874= (c.2622C>T) in the general population?

DCTN1 p.Ser874= (c.2622C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

DCTN1 p.Ser874=

c.2622C>T · rs1367060889 · VCV1402096

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

DCTN1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.61	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.46	GERP 0.14, phastCons 0.032
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,866 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000752% 11/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,955
South Asian	0.00329%	30,360
European (non-Finnish)	0.000424%	236,004

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.Ser874=
Coding: c.2622C>T
MANE Select: NM_004082
dbSNP: rs1367060889
Type: single nucleotide variant
Location: chr2:74366465 (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

DCTN1-related disorder

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

Similar variants

DCTN1 p.Ser874Arg 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-ser874 (accessed [today's date]).

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