Is DYNC2H1 p.Gln4231= (c.12693A>G) pathogenic?

DYNC2H1 p.Gln4231= (c.12693A>G) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-17). Very rare (popmax 0.00729%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Gln4231= (c.12693A>G)?

DYNC2H1 p.Gln4231= (c.12693A>G) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Gln4231= (c.12693A>G) in the general population?

DYNC2H1 p.Gln4231= (c.12693A>G) is very rare (popmax 0.00729%, nfe) (gnomAD).

DYNC2H1 p.Gln4231=

c.12693A>G · rs371640317 · VCV880133

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00729%, 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 0.48	GERP -3.5, phastCons 0.14
Overall
CADD	0.449	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,179,742 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00545% 88/1,613,742 alleles · very rare exomes 88/1,461,432 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,718
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Gln4231=
Coding: c.12693A>G
MANE Select: NM_001377
dbSNP: rs371640317
Type: single nucleotide variant
Location: chr11:103468633 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4231: a β-strand

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-gln4231 (accessed [today's date]).

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