Is DYNC2H1 p.Ile4002= (c.12006C>T) pathogenic?

DYNC2H1 p.Ile4002= (c.12006C>T) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0165%, mid); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ile4002= (c.12006C>T)?

DYNC2H1 p.Ile4002= (c.12006C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ile4002= (c.12006C>T) in the general population?

DYNC2H1 p.Ile4002= (c.12006C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

DYNC2H1 p.Ile4002=

c.12006C>T · rs775505863 · VCV198954

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Jeune syndrome

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 -3.5	GERP -4.3
Overall
CADD	1.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,068 alleles

Filtering AF 0.00708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0066%

Overall 0.00744% 120/1,612,392 alleles · ultra-rare exomes 108/1,460,346 · genomes 12/152,046 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,068
Remaining individualsnot grpmax-eligible	0.0128%	7,799
Admixed American	0.0117%	8,563
European (non-Finnish)	0.00848%	11,791
African / African-American	0.00267%	37,422
East Asian	0.00223%	44,812
South Asian	0.0011%	90,860

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: DYNC2H1
Protein: p.Ile4002=
Coding: c.12006C>T
MANE Select: NM_001377
dbSNP: rs775505863
Type: single nucleotide variant
Location: chr11:103323957 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4002: an α-helix

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same condition
DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same condition
DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.12457-1G>C Likely 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/dync2h1-p-ile4002 (accessed [today's date]).

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