Is DCTN1 p.Arg795His (c.2384G>A) pathogenic?

DCTN1 p.Arg795His (c.2384G>A) is classified Uncertain significance in DCTN1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-09). AlphaMissense: likely benign (0.1564); Very rare (popmax 0.005%, amr); Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with DCTN1 p.Arg795His (c.2384G>A)?

DCTN1 p.Arg795His (c.2384G>A) is associated with amyotrophic lateral sclerosis type 1, Perry syndrome, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Arg795His (c.2384G>A) in the general population?

DCTN1 p.Arg795His (c.2384G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DCTN1 p.Arg795His (c.2384G>A)?

AlphaMissense predicts likely benign (score 0.1564) — an in-silico prediction, not a clinical call.

DCTN1 p.Arg795His

c.2384G>A · rs377530504 · VCV652631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1564 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyotrophic lateral sclerosis type 1

Computational evidence

Protein change
AlphaMissense	0.1564	likely benign
REVEL	0.736	pathogenic-leaning
SaProt	LLR -8.01	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,200 bp · p 0.5 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 0.005% Admixed American · 3/60,002 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00142% 23/1,614,096 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00223%	44,900
African / African-American	0.00133%	74,924
European (non-Finnish)	0.00119%	84,289
South Asian	0.0011%	91,088

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.Arg795His
Coding: c.2384G>A
MANE Select: NM_004082
dbSNP: rs377530504
Type: single nucleotide variant
Location: chr2:74366865 (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.Arg795Cys 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-arg795his (accessed [today's date]).

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