Is DCTN4 p.Val366Ile (c.1096G>A) pathogenic?

DCTN4 p.Val366Ile (c.1096G>A) is classified Likely benign in DCTN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.0592); Very rare (popmax 0.00333%, amr).

How common is DCTN4 p.Val366Ile (c.1096G>A) in the general population?

DCTN4 p.Val366Ile (c.1096G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DCTN4 p.Val366Ile (c.1096G>A)?

AlphaMissense predicts likely benign (score 0.0592) — an in-silico prediction, not a clinical call.

DCTN4 p.Val366Ile

c.1096G>A · rs755936574 · VCV3080652

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0592	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -4
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.0058 · regional, not allelic
Overall
CADD	0.08	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 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00149% 24/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00267%	37,449
European (non-Finnish)	0.00144%	69,414
South Asian	0.0011%	91,086

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: DCTN4
Protein: p.Val366Ile
Coding: c.1096G>A
MANE Select: NM_016221
dbSNP: rs755936574
Type: single nucleotide variant
Location: chr5:150715638 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 84.78 · 2 PDB
Residue 366: a β-strand

Full DCTN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCTN4 p.Ala195Thr Uncertain significance ★ ⚠ same type
DCTN4 p.Ala221Thr Uncertain significance ★ ⚠ same type
DCTN4 p.Ala22Val Uncertain significance ★ ⚠ same type
DCTN4 p.Ala2Ser Uncertain significance ★ ⚠ same type
DCTN4 p.Arg143Trp Uncertain significance ★ ⚠ same type
DCTN4 p.Arg162Gln Uncertain significance ★ ⚠ same type
DCTN4 p.Arg169Gln Uncertain significance ★ ⚠ same type
DCTN4 p.Arg192Gln Uncertain significance ★ ⚠ same type

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/dctn4-p-val366ile (accessed [today's date]).

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