Is DYNC2I2 p.Ser410= (c.1230C>T) pathogenic?

DYNC2I2 p.Ser410= (c.1230C>T) is classified Likely benign in DYNC2I2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-05). Very rare (popmax 0.0027%, afr); Associated with DYNC2I2-related disorder.

What condition is associated with DYNC2I2 p.Ser410= (c.1230C>T)?

DYNC2I2 p.Ser410= (c.1230C>T) is associated with DYNC2I2-related disorder (ClinVar).

How common is DYNC2I2 p.Ser410= (c.1230C>T) in the general population?

DYNC2I2 p.Ser410= (c.1230C>T) is very rare (popmax 0.0027%, afr) (gnomAD).

DYNC2I2 p.Ser410=

c.1230C>T · rs146817584 · VCV3057856

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Conditions

DYNC2I2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -3
Overall
CADD	0.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0027% African / African-American · 2/74,120 alleles

Filtering AF 0.000448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000627% 10/1,594,854 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,060
East Asian	0.00223%	44,818
Remaining individualsnot grpmax-eligible	0.00162%	61,602
European (non-Finnish)	0.000512%	195,299

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.Ser410=
Coding: c.1230C>T
MANE Select: NM_052844
dbSNP: rs146817584
Type: single nucleotide variant
Location: chr9:128634368 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB
Residue 410: a UniProt-annotated variant site (in srtd11)

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.Gly293Trp Uncertain significance ★ ⚠ same condition
DYNC2I2 p.His391Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
DYNC2I2 c.*8C>T 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-ser410 (accessed [today's date]).

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