Is DYNC2H1 p.Asp2059= (c.6177C>T) pathogenic?

DYNC2H1 p.Asp2059= (c.6177C>T) is classified Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-08). Ultra-rare (popmax 0.0331%, mid); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Asp2059= (c.6177C>T)?

DYNC2H1 p.Asp2059= (c.6177C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Asp2059= (c.6177C>T) in the general population?

DYNC2H1 p.Asp2059= (c.6177C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

DYNC2H1 p.Asp2059=

c.6177C>T · rs180806841 · VCV695217

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, 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 0.54	GERP -2.8, phastCons 1
Overall
CADD	4.903	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,050 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00199% 32/1,612,072 alleles · ultra-rare exomes 29/1,460,084 · genomes 3/151,988 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.0128%	7,796
Admixed American	0.00834%	11,987
South Asian	0.0077%	12,988
African / African-American	0.00267%	37,465
European (non-Finnish)	0.000679%	147,338

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.Asp2059=
Coding: c.6177C>T
MANE Select: NM_001377
dbSNP: rs180806841
Type: single nucleotide variant
Location: chr11:103179063 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2059: the 'aaa 2' 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-asp2059 (accessed [today's date]).

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