Is DYNC2H1 p.Asp7= (c.21C>T) pathogenic?

DYNC2H1 p.Asp7= (c.21C>T) is classified Benign/Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Asp7= (c.21C>T)?

DYNC2H1 p.Asp7= (c.21C>T) is associated with asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

DYNC2H1 p.Asp7=

Q: How common is DYNC2H1 p.Asp7= (c.21C>T) in the general population?

DYNC2H1 p.Asp7= (c.21C>T) is common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.21C>T · rs17301028 · VCV301995

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 12.6%, mid) — too common for a highly-penetrant pathogenic allele

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 0.7	GERP -0.55, phastCons 1
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.6% Middle Eastern · 766/6,060 alleles

Filtering AF 11.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.6%

Overall 8.7% 140,351/1,613,576 alleles · common exomes 130,393/1,461,330 · genomes 9,958/152,246 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	13.7%	7
Middle Easterngrpmax	12.6%	8
European (non-Finnish)	9.66%	10
South Asian	9.4%	11
Remaining individualsnot grpmax-eligible	8.59%	12
Admixed American	5.68%	18
Amishnot grpmax-eligible	5.15%	19
Finnishnot grpmax-eligible	4.56%	22
African / African-American	1.67%	60
East Asian	0.029%	3,453

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp7=
Coding: c.21C>T
MANE Select: NM_001377
dbSNP: rs17301028
Type: single nucleotide variant
Location: chr11:103109595 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 7: the 'stem' region

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-asp7 (accessed [today's date]).

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