Is DYNC2H1 p.Leu11= (c.33C>T) pathogenic?

DYNC2H1 p.Leu11= (c.33C>T) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0887%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Leu11= (c.33C>T)?

DYNC2H1 p.Leu11= (c.33C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Leu11= (c.33C>T) in the general population?

DYNC2H1 p.Leu11= (c.33C>T) is ultra-rare (popmax 0.0887%, nfe) (gnomAD).

DYNC2H1 p.Leu11=

c.33C>T · rs373977008 · VCV193155

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0887%, nfe)

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 -1	GERP -4.7, phastCons 0.001
Overall
CADD	6.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0887% European (non-Finnish) · 1,046/1,179,878 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0823%

Overall 0.0668% 1,078/1,613,962 alleles · ultra-rare exomes 997/1,461,646 · genomes 81/152,316 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0887%	1,128
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.008%	12,507
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00167%	60,026

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.Leu11=
Coding: c.33C>T
MANE Select: NM_001377
dbSNP: rs373977008
Type: single nucleotide variant
Location: chr11:103109607 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 11: the 'stem' 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

Also linked: asphyxiating thoracic dystrophy 3

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.12156+1G>A Pathogenic/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-leu11 (accessed [today's date]).

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