Is DYNC2I2 p.Thr354Ala (c.1060A>G) pathogenic?

DYNC2I2 p.Thr354Ala (c.1060A>G) is classified Pathogenic/Likely pathogenic in DYNC2I2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2017-06-01). AlphaMissense: likely benign (0.1377); Absent from gnomAD v4.1; Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2I2 p.Thr354Ala (c.1060A>G)?

DYNC2I2 p.Thr354Ala (c.1060A>G) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2I2 p.Thr354Ala (c.1060A>G) in the general population?

DYNC2I2 p.Thr354Ala (c.1060A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2I2 p.Thr354Ala (c.1060A>G)?

AlphaMissense predicts likely benign (score 0.1377) — an in-silico prediction, not a clinical call.

DYNC2I2 p.Thr354Ala

c.1060A>G · rs1554771066 · VCV446623

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1377 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
AlphaMissense	0.1377	likely benign ⚠ discordant with ClinVar
REVEL	0.108	moderately benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.59 · regional, not allelic
Overall
CADD	19.64	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

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.Thr354Ala
Coding: c.1060A>G
MANE Select: NM_052844
dbSNP: rs1554771066
Type: single nucleotide variant
Location: chr9:128634843 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB
Residue 354: a UniProt-annotated variant site (in srtd11)

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

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I2 p.Thr354Met Conflicting classifications of pathogenicity ★ ⚠ same residue
DYNC2I2 p.Thr354= Likely benign ★ same residue
DYNC2I2 p.Gln466Pro Pathogenic/Likely pathogenic ⚠ same condition
DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same type
DYNC2I2 p.Arg121Ter Pathogenic ★★ same type
DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
DYNC2I2 p.Arg447Trp Pathogenic/Likely pathogenic ★★ same type
DYNC2I2 p.Ala131Val 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/dync2i2-p-thr354ala (accessed [today's date]).

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