Is DYNC2H1 p.Ala3666= (c.10998A>G) pathogenic?

DYNC2H1 p.Ala3666= (c.10998A>G) is classified Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-16). Very rare (popmax 0.00212%, nfe); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Ala3666= (c.10998A>G)?

DYNC2H1 p.Ala3666= (c.10998A>G) is associated with asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ala3666= (c.10998A>G) in the general population?

DYNC2H1 p.Ala3666= (c.10998A>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

DYNC2H1 p.Ala3666=

c.10998A>G · rs758373368 · VCV994100

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00212%, 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 0.68	GERP -1.2, phastCons 0.89
Overall
CADD	6.441	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,558 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00174% 28/1,612,482 alleles · very rare exomes 25/1,460,260 · genomes 3/152,222 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,182
Admixed American	0.00167%	59,794
Remaining individualsnot grpmax-eligible	0.0016%	62,420
South Asian	0.00111%	90,390

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.Ala3666=
Coding: c.10998A>G
MANE Select: NM_001377
dbSNP: rs758373368
Type: single nucleotide variant
Location: chr11:103286362 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3666: an α-helix

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-ala3666 (accessed [today's date]).

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