Is DYNC2H1 p.Ile3311= (c.9933C>T) pathogenic?

DYNC2H1 p.Ile3311= (c.9933C>T) is classified Likely benign in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Ultra-rare (popmax 0.0256%, sas); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ile3311= (c.9933C>T)?

DYNC2H1 p.Ile3311= (c.9933C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ile3311= (c.9933C>T) in the general population?

DYNC2H1 p.Ile3311= (c.9933C>T) is ultra-rare (popmax 0.0256%, sas) (gnomAD).

DYNC2H1 p.Ile3311=

c.9933C>T · rs745405817 · VCV2917595

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0256%, sas)

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 0.05	GERP -0.74, phastCons 0.86
Overall
CADD	7.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0256% South Asian · 21/82,030 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.00169% 26/1,540,984 alleles · ultra-rare exomes 23/1,388,878 · genomes 3/152,106 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0256%	3,906
Remaining individualsnot grpmax-eligible	0.00836%	11,955

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.Ile3311=
Coding: c.9933C>T
MANE Select: NM_001377
dbSNP: rs745405817
Type: single nucleotide variant
Location: chr11:103245265 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3311: an α-helix; the 'aaa 5' region

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-ile3311 (accessed [today's date]).

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