Is DYNC2H1 p.Ser4109= (c.12327A>G) pathogenic?

DYNC2H1 p.Ser4109= (c.12327A>G) is classified Likely benign in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Very rare (popmax 0.00669%, eas); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ser4109= (c.12327A>G)?

DYNC2H1 p.Ser4109= (c.12327A>G) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ser4109= (c.12327A>G) in the general population?

DYNC2H1 p.Ser4109= (c.12327A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

DYNC2H1 p.Ser4109=

c.12327A>G · rs746071031 · VCV2720294

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.42	GERP -0.67, phastCons 0.001
Overall
CADD	3.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,862 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00112% 18/1,613,770 alleles · very rare exomes 16/1,461,522 · genomes 2/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,954
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.0011%	90,758

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.Ser4109=
Coding: c.12327A>G
MANE Select: NM_001377
dbSNP: rs746071031
Type: single nucleotide variant
Location: chr11:103399833 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4109: an α-helix

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-ser4109 (accessed [today's date]).

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