Is DCTN1 p.Arg803Ser (c.2409G>T) pathogenic?

DCTN1 p.Arg803Ser (c.2409G>T) is classified Uncertain significance in DCTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-13). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1; Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with DCTN1 p.Arg803Ser (c.2409G>T)?

DCTN1 p.Arg803Ser (c.2409G>T) is associated with amyotrophic lateral sclerosis type 1, Perry syndrome, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Arg803Ser (c.2409G>T) in the general population?

DCTN1 p.Arg803Ser (c.2409G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCTN1 p.Arg803Ser (c.2409G>T)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

DCTN1 p.Arg803Ser

c.2409G>T · VCV4793849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyotrophic lateral sclerosis type 1

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic · top 2% in DCTN1
REVEL	0.731	pathogenic-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -0.002, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 3,200 bp · p 0.5 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCTN1
Protein: p.Arg803Ser
Coding: c.2409G>T
MANE Select: NM_004082
Type: single nucleotide variant
Location: chr2:74366840 (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 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-arg803ser (accessed [today's date]).

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