Is DCTN1 p.Arg502Ser (c.1504C>A) pathogenic?

DCTN1 p.Arg502Ser (c.1504C>A) is classified Benign/Likely benign in DCTN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.3685); Rare (popmax 0.253%, afr); Associated with Inborn genetic diseases.

What condition is associated with DCTN1 p.Arg502Ser (c.1504C>A)?

DCTN1 p.Arg502Ser (c.1504C>A) is associated with Inborn genetic diseases, amyotrophic lateral sclerosis type 1, Perry syndrome (ClinVar).

How common is DCTN1 p.Arg502Ser (c.1504C>A) in the general population?

DCTN1 p.Arg502Ser (c.1504C>A) is rare (popmax 0.253%, afr) (gnomAD).

What do computational predictors say about DCTN1 p.Arg502Ser (c.1504C>A)?

AlphaMissense predicts ambiguous (score 0.3685) — an in-silico prediction, not a clinical call.

DCTN1 p.Arg502Ser

c.1504C>A · rs145958900 · VCV706130

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3685 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.253%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3685	ambiguous
REVEL	0.433	indeterminate
SaProt	LLR -5.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,940 bp · p 6.9e-06 · regional, not allelic
Overall
CADD	26.6	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 0.253% African / African-American · 190/75,046 alleles

Filtering AF 0.224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.0134% 216/1,614,192 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.253%	395
Admixed American	0.025%	4,002
Remaining individualsnot grpmax-eligible	0.016%	6,251
European (non-Finnish)	8.47e-05%	1,180,036

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.Arg502Ser
Coding: c.1504C>A
MANE Select: NM_004082
dbSNP: rs145958900
Type: single nucleotide variant
Location: chr2:74369380 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 1 Perry syndrome neuronopathy, distal hereditary motor, type 7B

Similar variants

DCTN1 p.Arg502Cys Uncertain significance ★★ ⚠ same residue
DCTN1 p.Arg502His 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

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-arg502ser (accessed [today's date]).

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