Is DCTN1 p.Glu1237= (c.3711G>A) pathogenic?

DCTN1 p.Glu1237= (c.3711G>A) is classified Benign in DCTN1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-14). Ultra-rare (popmax 0.0527%, sas); Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with DCTN1 p.Glu1237= (c.3711G>A)?

DCTN1 p.Glu1237= (c.3711G>A) is associated with amyotrophic lateral sclerosis type 1, peripheral neuropathy, Perry syndrome (ClinVar).

How common is DCTN1 p.Glu1237= (c.3711G>A) in the general population?

DCTN1 p.Glu1237= (c.3711G>A) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

DCTN1 p.Glu1237=

c.3711G>A · rs747638337 · VCV1703705

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

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 -0.088	GERP -2.8, phastCons 0.53
Overall
CADD	4.805	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0527% South Asian · 48/91,092 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.0031% 50/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0527%	1,898
Middle Eastern	0.0164%	6,084
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.Glu1237=
Coding: c.3711G>A
MANE Select: NM_004082
dbSNP: rs747638337
Type: single nucleotide variant
Location: chr2:74361625 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 13 PDB
Residue 1237: the 'interaction with hps6' region; an α-helix

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: peripheral neuropathy Perry syndrome neuronopathy, distal hereditary motor, type 7B

Similar variants

DCTN1 p.Glu1237Lys 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-glu1237 (accessed [today's date]).

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