Is DYNC1H1 p.Cys792= (c.2376C>T) pathogenic?

DYNC1H1 p.Cys792= (c.2376C>T) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-28). Ultra-rare (popmax 0.0329%, mid); Associated with autosomal dominant cerebellar ataxia.

How common is DYNC1H1 p.Cys792= (c.2376C>T) in the general population?

DYNC1H1 p.Cys792= (c.2376C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

DYNC1H1 p.Cys792=

Q: What condition is associated with DYNC1H1 p.Cys792= (c.2376C>T)?

DYNC1H1 p.Cys792= (c.2376C>T) is associated with autosomal dominant cerebellar ataxia, autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

c.2376C>T · rs35092963 · VCV516911

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

autosomal dominant cerebellar ataxia

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 -8.9	GERP -4.6
Overall
CADD	2.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00682% 110/1,613,118 alleles · ultra-rare exomes 99/1,461,050 · genomes 11/152,068 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.0307%	3,252
Remaining individualsnot grpmax-eligible	0.00801%	12,491
European (non-Finnish)	0.00594%	16,847
African / African-American	0.00401%	24,953
Admixed American	0.00334%	29,978

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: DYNC1H1
Protein: p.Cys792=
Coding: c.2376C>T
MANE Select: NM_001376
dbSNP: rs35092963
Type: single nucleotide variant
Location: chr14:101986601 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 792: an α-helix; the 'stem' region; the 'interaction with dync1li2' region

Full DYNC1H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures Charcot-Marie-Tooth disease axonal type 2O cortical dysplasia, complex, with other brain malformations 13

Similar variants

DYNC1H1 p.Cys792Gly Conflicting classifications of pathogenicity ★ same residue
DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Trp Pathogenic ★★ same condition
DYNC1H1 p.Arg1962Cys Pathogenic ★★ same condition
DYNC1H1 p.Arg1962His Likely pathogenic ★★ same condition
DYNC1H1 p.Arg2332Cys Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg2492Ter 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/dync1h1-p-cys792 (accessed [today's date]).

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