Is DYNC2H1 p.Pro1814= (c.5442C>T) pathogenic?

DYNC2H1 p.Pro1814= (c.5442C>T) is classified Benign/Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.54%, afr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Pro1814= (c.5442C>T)?

DYNC2H1 p.Pro1814= (c.5442C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Pro1814= (c.5442C>T) in the general population?

DYNC2H1 p.Pro1814= (c.5442C>T) is low-frequency (popmax 1.54%, afr) (gnomAD).

DYNC2H1 p.Pro1814=

c.5442C>T · rs76833922 · VCV220052

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, afr)

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 0.18	GERP -3.9, phastCons 0.18
Overall
CADD	8.459	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.54% African / African-American · 1,137/74,014 alleles

Filtering AF 1.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.43%

Overall 0.0802% 1,283/1,599,590 alleles · low-frequency exomes 617/1,447,596 · genomes 666/151,994 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.54%	65
Remaining individualsnot grpmax-eligible	0.0971%	1,030
Admixed American	0.0686%	1,457
Middle Eastern	0.0664%	1,507
South Asian	0.00449%	22,264
European (non-Finnish)	0.00315%	31,703
Finnishnot grpmax-eligible	0.00157%	63,628

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.Pro1814=
Coding: c.5442C>T
MANE Select: NM_001377
dbSNP: rs76833922
Type: single nucleotide variant
Location: chr11:103173189 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1814: a β-strand; the 'aaa 1' 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-pro1814 (accessed [today's date]).

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