Is DYNC2H1 p.Val2403= (c.7209G>A) pathogenic?

DYNC2H1 p.Val2403= (c.7209G>A) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.022%, nfe); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Val2403= (c.7209G>A)?

DYNC2H1 p.Val2403= (c.7209G>A) is associated with asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Val2403= (c.7209G>A) in the general population?

DYNC2H1 p.Val2403= (c.7209G>A) is ultra-rare (popmax 0.022%, nfe) (gnomAD).

DYNC2H1 p.Val2403=

c.7209G>A · rs371948128 · VCV698582

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, nfe)

Conditions

asphyxiating thoracic dystrophy 3

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 0.98	GERP -0.048, phastCons 1
Overall
CADD	4.911	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% European (non-Finnish) · 259/1,177,960 alleles

Filtering AF 0.0197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.0171% 275/1,610,552 alleles · ultra-rare exomes 254/1,458,608 · genomes 21/151,944 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.022%	4,548
Remaining individualsnot grpmax-eligible	0.0112%	8,897
Admixed American	0.00835%	11,975
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,516
East Asian	0.00224%	44,662
Finnishnot grpmax-eligible	0.00157%	63,846
South Asian	0.0011%	90,636

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.Val2403=
Coding: c.7209G>A
MANE Select: NM_001377
dbSNP: rs371948128
Type: single nucleotide variant
Location: chr11:103188565 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2403: a β-strand; the 'aaa 3' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Jeune syndrome

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-val2403 (accessed [today's date]).

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