Is DYNC2H1 p.Ile1604= (c.4812C>T) pathogenic?

DYNC2H1 p.Ile1604= (c.4812C>T) is classified Benign/Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.295%, afr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ile1604= (c.4812C>T)?

DYNC2H1 p.Ile1604= (c.4812C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ile1604= (c.4812C>T) in the general population?

DYNC2H1 p.Ile1604= (c.4812C>T) is rare (popmax 0.295%, afr) (gnomAD).

DYNC2H1 p.Ile1604=

c.4812C>T · rs370677208 · VCV695762

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.295%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 0.91, phastCons 1
Overall
CADD	7.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.295% African / African-American · 221/74,982 alleles

Filtering AF 0.263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.25%

Overall 0.0144% 233/1,613,154 alleles · rare exomes 109/1,460,972 · genomes 124/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.295%	339
Middle Eastern	0.0166%	6,018
Remaining individualsnot grpmax-eligible	0.0128%	7,807
Admixed American	0.00167%	59,978
South Asian	0.0011%	91,048
European (non-Finnish)	8.48e-05%	1,179,505

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.Ile1604=
Coding: c.4812C>T
MANE Select: NM_001377
dbSNP: rs370677208
Type: single nucleotide variant
Location: chr11:103168804 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1604: the 'stem' region; 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-ile1604 (accessed [today's date]).

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