Is DYNC2I2 p.His82fs (c.245_246del) pathogenic?

DYNC2I2 p.His82fs (c.245246del) is classified Pathogenic in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-14). Very rare (popmax 0.00017%, nfe); Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.His82fs (c.245_246del)?

DYNC2I2 p.His82fs (c.245_246del) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.His82fs (c.245_246del) in the general population?

DYNC2I2 p.His82fs (c.245_246del) is very rare (popmax 0.00017%, nfe) (gnomAD).

DYNC2I2 p.His82fs

c.245_246del · rs1860503169 · VCV2135286

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

short-rib thoracic dysplasia 11 with or without polydactyly

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 2 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -1.8, phastCons 0.007
Overall
CADD	16.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,592 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,226 alleles · very rare

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.His82fs
Coding: c.245_246del
MANE Select: NM_052844
dbSNP: rs1860503169
Type: Deletion
Location: chr9:128640880 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB
Residue 82: the 'dynll2 binding' region

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 p.Leu438fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Phe439fs Pathogenic ★★ same condition
DYNC2I2 p.Pro210fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Pro32fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 c.1372+5del Uncertain significance ★★ same condition
DYNC2I2 c.546-1_547del Likely pathogenic ★ same condition
DYNC2I2 p.Gln504_Gly505insTer Pathogenic ★ same condition
DYNC2I2 p.Gln86fs Pathogenic ★ 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-his82fs (accessed [today's date]).

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