Is DYNC2H1 p.Arg796= (c.2386C>A) pathogenic?

DYNC2H1 p.Arg796= (c.2386C>A) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-06-21). Very rare (popmax 0.00017%, nfe); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Arg796= (c.2386C>A)?

DYNC2H1 p.Arg796= (c.2386C>A) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Arg796= (c.2386C>A) in the general population?

DYNC2H1 p.Arg796= (c.2386C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

DYNC2H1 p.Arg796=

c.2386C>A · VCV4530603

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 0.00017%, nfe)

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	acceptor loss, 40 bp away · masked 0 · deltas
Pangolin	Δ0.25	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Overall
CADD	9.198	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,352 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,610,878 alleles · very rare exomes 3/1,458,764 · genomes 0/152,114 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00157%	63,816
European (non-Finnish)grpmax	0.00017%	589,175

Finnish 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.Arg796=
Coding: c.2386C>A
MANE Select: NM_001377
Type: single nucleotide variant
Location: chr11:103135760 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 796: 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

Similar variants

DYNC2H1 p.Arg796Trp Uncertain significance ★★ same residue
DYNC2H1 p.Arg796Leu Uncertain significance ★ same residue
DYNC2H1 p.Arg796Gln Uncertain significance ★★ 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.12156+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-arg796 (accessed [today's date]).

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