Is DCTN1 p.Ser23= (c.69C>T) pathogenic?

DCTN1 p.Ser23= (c.69C>T) is classified Likely benign in DCTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-06). Very rare (popmax 0.00267%, afr); Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with DCTN1 p.Ser23= (c.69C>T)?

DCTN1 p.Ser23= (c.69C>T) is associated with amyotrophic lateral sclerosis type 1, Perry syndrome, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Ser23= (c.69C>T) in the general population?

DCTN1 p.Ser23= (c.69C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

DCTN1 p.Ser23=

c.69C>T · rs1430177390 · VCV2929602

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

amyotrophic lateral sclerosis type 1

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 -2.9	GERP -5.2
Overall
CADD	3.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,954 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,611,266 alleles · very rare exomes 5/1,459,010 · genomes 2/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,477
Admixed American	0.00167%	60,012
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,345

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.Ser23=
Coding: c.69C>T
MANE Select: NM_004082
dbSNP: rs1430177390
Type: single nucleotide variant
Location: chr2:74378210 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 13 PDB
Residue 23: the 'disordered' region

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

Disease context

amyotrophic lateral sclerosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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-ser23 (accessed [today's date]).

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