Is DYNC2H1 p.His3410= (c.10230T>C) pathogenic?

DYNC2H1 p.His3410= (c.10230T>C) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00234%, eas); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.His3410= (c.10230T>C)?

DYNC2H1 p.His3410= (c.10230T>C) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.His3410= (c.10230T>C) in the general population?

DYNC2H1 p.His3410= (c.10230T>C) is very rare (popmax 0.00234%, eas) (gnomAD).

DYNC2H1 p.His3410=

c.10230T>C · rs1279419542 · VCV880028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00234%, eas)

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 2.8	GERP 0.62, phastCons 1
Overall
CADD	7.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00234% East Asian · 1/42,692 alleles

Overall 6.39e-05% 1/1,565,864 alleles · very rare exomes 1/1,413,574 · genomes 0/152,290 · joint denominator

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.His3410=
Coding: c.10230T>C
MANE Select: NM_001377
dbSNP: rs1279419542
Type: single nucleotide variant
Location: chr11:103255438 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3410: an α-helix; the 'aaa 5' 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 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
DYNC2H1 c.1662-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.2106+2T>C Likely pathogenic ★★ same condition
DYNC2H1 c.2574+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-his3410 (accessed [today's date]).

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