Is DYNC2I1 p.Pro964fs (c.2890_2911del) pathogenic?

DYNC2I1 p.Pro964fs (c.28902911del) is classified Likely pathogenic in DYNC2I1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-29). Very rare (popmax 0.000254%, nfe); Associated with WDR60-related disorders.

What condition is associated with DYNC2I1 p.Pro964fs (c.2890_2911del)?

DYNC2I1 p.Pro964fs (c.2890_2911del) is associated with WDR60-related disorders (ClinVar).

How common is DYNC2I1 p.Pro964fs (c.2890_2911del) in the general population?

DYNC2I1 p.Pro964fs (c.2890_2911del) is very rare (popmax 0.000254%, nfe) (gnomAD).

DYNC2I1 p.Pro964fs

c.2890_2911del · VCV4898772

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

WDR60-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 24 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,790 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,488 alleles · very rare exomes 3/1,461,134 · genomes 0/152,354 · 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: DYNC2I1
Protein: p.Pro964fs
Coding: c.2890_2911del
MANE Select: NM_018051
Type: Deletion
Location: chr7:158942033 (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 964: a UniProt-annotated variant site (in srtd8; reduces interaction with ift proteins); a UniProt-annotated variant site (in srtd8)

Full DYNC2I1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

WDR60-related disorders

Similar variants

DYNC2I1 p.Arg185fs Likely pathogenic ★ same condition
DYNC2I1 c.573+1G>A Likely pathogenic ★ same condition
DYNC2I1 p.Arg109Ter Likely pathogenic ★ same condition
DYNC2I1 p.Asn527fs Pathogenic ★ same condition
DYNC2I1 p.Gly932Arg Uncertain significance ⚠ same condition
DYNC2I1 p.His297Gln Uncertain significance ⚠ same condition
DYNC2I1 p.Leu765Pro Uncertain significance ⚠ same condition
DYNC2I1 c.1358-789G>A Benign 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-pro964fs (accessed [today's date]).

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