Is DCTN1 p.Arg331Gln (c.992G>A) pathogenic?

DCTN1 p.Arg331Gln (c.992G>A) is classified Uncertain significance in DCTN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-27). AlphaMissense: likely benign (0.0976); Very rare (popmax 0.004%, afr); Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with DCTN1 p.Arg331Gln (c.992G>A)?

DCTN1 p.Arg331Gln (c.992G>A) is associated with amyotrophic lateral sclerosis type 1, Perry syndrome, neuronopathy, distal hereditary motor, type 7B (ClinVar).

How common is DCTN1 p.Arg331Gln (c.992G>A) in the general population?

DCTN1 p.Arg331Gln (c.992G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DCTN1 p.Arg331Gln (c.992G>A)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

DCTN1 p.Arg331Gln

c.992G>A · rs773056643 · VCV2921882

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

amyotrophic lateral sclerosis type 1

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,940 bp · p 6.9e-06 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,070 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000958% 14/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,023
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,255
East Asian	0.00223%	44,888
South Asian	0.0011%	91,078
European (non-Finnish)	0.000508%	196,674

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.Arg331Gln
Coding: c.992G>A
MANE Select: NM_004082
dbSNP: rs773056643
Type: single nucleotide variant
Location: chr2:74370677 (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.Arg331Trp Uncertain significance ★★ ⚠ same residue
DCTN1 p.Arg331= Likely benign ★ 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-arg331gln (accessed [today's date]).

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