Is DYNC2I1 p.Ile799= (c.2397C>T) pathogenic?

DYNC2I1 p.Ile799= (c.2397C>T) is classified Benign/Likely benign in DYNC2I1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-20). Rare (popmax 0.51%, afr); Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

What condition is associated with DYNC2I1 p.Ile799= (c.2397C>T)?

DYNC2I1 p.Ile799= (c.2397C>T) is associated with short-rib thoracic dysplasia 8 with or without polydactyly (ClinVar).

How common is DYNC2I1 p.Ile799= (c.2397C>T) in the general population?

DYNC2I1 p.Ile799= (c.2397C>T) is rare (popmax 0.51%, afr) (gnomAD).

DYNC2I1 p.Ile799=

c.2397C>T · rs116197118 · VCV766804

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.51%, afr)

Conditions

short-rib thoracic dysplasia 8 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor loss, 25 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -9	GERP -4.6
Overall
CADD	1.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.51% African / African-American · 383/75,066 alleles

Filtering AF 0.468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.452%

Overall 0.0269% 434/1,613,438 alleles · rare exomes 216/1,461,066 · genomes 218/152,372 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.51%	196
Remaining individualsnot grpmax-eligible	0.024%	4,165
Admixed American	0.02%	4,991
East Asian	0.00446%	22,438
South Asian	0.0044%	22,738
European (non-Finnish)	0.00153%	65,535

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.Ile799=
Coding: c.2397C>T
MANE Select: NM_018051
dbSNP: rs116197118
Type: single nucleotide variant
Location: chr7:158926427 (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 799: 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

short-rib thoracic dysplasia 8 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I1 p.Ile799Val Benign ★★ same residue
DYNC2I1 p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg441Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg642Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg762Ter Pathogenic ★★ same condition
DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala609Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala800Thr 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/dync2i1-p-ile799 (accessed [today's date]).

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