Is DYNC2I1 p.Glu286Asp (c.858G>T) pathogenic?

DYNC2I1 p.Glu286Asp (c.858G>T) is classified Uncertain significance in DYNC2I1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely benign (0.0911); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYNC2I1 p.Glu286Asp (c.858G>T)?

DYNC2I1 p.Glu286Asp (c.858G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2I1 p.Glu286Asp (c.858G>T) in the general population?

DYNC2I1 p.Glu286Asp (c.858G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2I1 p.Glu286Asp (c.858G>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

DYNC2I1 p.Glu286Asp

c.858G>T · rs2535900080 · VCV3086533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.68	GERP -3.3
Regional constraint	o/e 0.98	unconstrained · MANE · 89 kb · p 0.52 · regional, not allelic
Overall
CADD	0.892	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

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: DYNC2I1
Protein: p.Glu286Asp
Coding: c.858G>T
MANE Select: NM_018051
dbSNP: rs2535900080
Type: single nucleotide variant
Location: chr7:158879968 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.87 · 4 PDB
Residue 286: the 'disordered' region

Full DYNC2I1 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

Similar variants

DYNC2I1 p.Glu286Lys Uncertain significance ★★ ⚠ same residue
DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala822Thr Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala956Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Arg1038Trp Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Arg149Cys Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Arg162Leu 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/dync2i1-p-glu286asp (accessed [today's date]).

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