Is DYNC2I2 p.Gly393Asp (c.1178G>A) pathogenic?

DYNC2I2 p.Gly393Asp (c.1178G>A) is classified Uncertain significance in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-09). AlphaMissense: likely pathogenic (0.8541); Very rare (popmax 6.29e-05%); Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Gly393Asp (c.1178G>A)?

DYNC2I2 p.Gly393Asp (c.1178G>A) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Gly393Asp (c.1178G>A) in the general population?

DYNC2I2 p.Gly393Asp (c.1178G>A) is very rare (popmax 6.29e-05%) (gnomAD).

What do computational predictors say about DYNC2I2 p.Gly393Asp (c.1178G>A)?

AlphaMissense predicts likely pathogenic (score 0.8541) — an in-silico prediction, not a clinical call.

DYNC2I2 p.Gly393Asp

c.1178G>A · rs1181220796 · VCV2015481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.29e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

short-rib thoracic dysplasia 11 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.8541	likely pathogenic · top 8% in DYNC2I2
REVEL	0.606	indeterminate
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.59 · regional, not allelic
Overall
CADD	25.2	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 6.29e-05%

Overall 6.29e-05% 1/1,589,880 alleles · very rare exomes 1/1,437,580 · genomes 0/152,300 · joint denominator

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: DYNC2I2
Protein: p.Gly393Asp
Coding: c.1178G>A
MANE Select: NM_052844
dbSNP: rs1181220796
Type: single nucleotide variant
Location: chr9:128634725 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB
Residue 393: a UniProt-annotated variant site (in srtd11)

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

Disease context

short-rib thoracic dysplasia 11 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Arg121Ter Pathogenic ★★ same condition
DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
DYNC2I2 p.Arg447Trp Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Ala131Val Uncertain significance ★★ ⚠ same condition
DYNC2I2 p.Ala13Gly Uncertain significance ★★ ⚠ same condition
DYNC2I2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
DYNC2I2 p.Ala369Val 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/dync2i2-p-gly393asp (accessed [today's date]).

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