Is DCTN1 p.Ala564= (c.1692C>T) pathogenic?

DCTN1 p.Ala564= (c.1692C>T) is classified Conflicting classifications of pathogenicity in DCTN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-01-15). Very rare (popmax 0.00267%, afr); Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with DCTN1 p.Ala564= (c.1692C>T)?

DCTN1 p.Ala564= (c.1692C>T) is associated with amyotrophic lateral sclerosis type 1, Perry syndrome, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Ala564= (c.1692C>T) in the general population?

DCTN1 p.Ala564= (c.1692C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

DCTN1 p.Ala564=

c.1692C>T · rs886043620 · VCV287304

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

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 1.7	GERP -2.4, phastCons 1
Overall
CADD	8.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,940 alleles

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

Overall 0.000248% 4/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,470
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	8.47e-05%	1,180,034

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.Ala564=
Coding: c.1692C>T
MANE Select: NM_004082
dbSNP: rs886043620
Type: single nucleotide variant
Location: chr2:74369107 (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

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 p.Ala564Ser 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-ala564 (accessed [today's date]).

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