Is DYNC2H1 p.Ala3445= (c.10335C>G) pathogenic?

DYNC2H1 p.Ala3445= (c.10335C>G) is classified Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-10). Very rare (popmax 0.00341%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ala3445= (c.10335C>G)?

DYNC2H1 p.Ala3445= (c.10335C>G) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ala3445= (c.10335C>G) in the general population?

DYNC2H1 p.Ala3445= (c.10335C>G) is very rare (popmax 0.00341%, nfe) (gnomAD).

DYNC2H1 p.Ala3445=

c.10335C>G · rs1383674031 · VCV2761208

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00341%, 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 -0.72	GERP -3.5, phastCons 0.008
Overall
CADD	4.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00341% European (non-Finnish) · 40/1,173,194 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.00256% 41/1,601,802 alleles · very rare exomes 39/1,449,802 · genomes 2/152,000 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00341%	29,330
African / African-American	0.00134%	74,650

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.Ala3445=
Coding: c.10335C>G
MANE Select: NM_001377
dbSNP: rs1383674031
Type: single nucleotide variant
Location: chr11:103256114 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3445: an α-helix; the 'aaa 5' 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

Similar variants

DYNC2H1 p.Ala3445fs Pathogenic ★ same residue
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

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-ala3445 (accessed [today's date]).

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