Is DYNC2I2 p.Gly293Trp (c.877G>T) pathogenic?

DYNC2I2 p.Gly293Trp (c.877G>T) is classified Uncertain significance in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-10). AlphaMissense: likely pathogenic (0.9674); Absent from gnomAD v4.1; Associated with DYNC2I2-related disorder.

What condition is associated with DYNC2I2 p.Gly293Trp (c.877G>T)?

DYNC2I2 p.Gly293Trp (c.877G>T) is associated with DYNC2I2-related disorder (ClinVar).

How common is DYNC2I2 p.Gly293Trp (c.877G>T) in the general population?

DYNC2I2 p.Gly293Trp (c.877G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2I2 p.Gly293Trp (c.877G>T)?

AlphaMissense predicts likely pathogenic (score 0.9674) — an in-silico prediction, not a clinical call.

DYNC2I2 p.Gly293Trp

c.877G>T · rs758829326 · VCV2630985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DYNC2I2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9674	likely pathogenic · top 2% in DYNC2I2
REVEL	0.637	indeterminate
SaProt	LLR -18.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.59 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DYNC2I2
Protein: p.Gly293Trp
Coding: c.877G>T
MANE Select: NM_052844
dbSNP: rs758829326
Type: single nucleotide variant
Location: chr9:128635196 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB

Full DYNC2I2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DYNC2I2-related disorder

Similar variants

DYNC2I2 p.Arg203Ter Likely pathogenic ★ same condition
DYNC2I2 p.His391Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
DYNC2I2 c.*8C>T Likely benign same condition
DYNC2I2 p.Ser410= Likely benign same condition
DYNC2I2 p.Leu438fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Thr514fs Likely pathogenic ★ same condition
DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same type
DYNC2I2 p.Arg121Ter Pathogenic ★★ 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/dync2i2-p-gly293trp (accessed [today's date]).

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