Is DYNC2H1 p.Val97= (c.291T>A) pathogenic?

DYNC2H1 p.Val97= (c.291T>A) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0101%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Val97= (c.291T>A)?

DYNC2H1 p.Val97= (c.291T>A) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3, inherited retinal dystrophy (ClinVar).

How common is DYNC2H1 p.Val97= (c.291T>A) in the general population?

DYNC2H1 p.Val97= (c.291T>A) is ultra-rare (popmax 0.0101%, nfe) (gnomAD).

DYNC2H1 p.Val97=

c.291T>A · rs377529350 · VCV301999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, 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 0.16	GERP -4.2, phastCons 0.99
Overall
CADD	5.922	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% European (non-Finnish) · 118/1,166,528 alleles

Filtering AF 0.0086% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00805%

Overall 0.00774% 122/1,575,934 alleles · ultra-rare exomes 107/1,423,904 · genomes 15/152,030 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0101%	9,886
Ashkenazi Jewishnot grpmax-eligible	0.00346%	28,884
Admixed American	0.00189%	52,772
Remaining individualsnot grpmax-eligible	0.00164%	60,888
South Asian	0.00123%	81,190

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.Val97=
Coding: c.291T>A
MANE Select: NM_001377
dbSNP: rs377529350
Type: single nucleotide variant
Location: chr11:103113632 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 97: 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 inherited retinal dystrophy

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-val97 (accessed [today's date]).

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