Is DYNC1H1 p.Ser784= (c.2352C>T) pathogenic?

DYNC1H1 p.Ser784= (c.2352C>T) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-11). Ultra-rare (popmax 0.0223%, eas); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Ser784= (c.2352C>T)?

DYNC1H1 p.Ser784= (c.2352C>T) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Ser784= (c.2352C>T) in the general population?

DYNC1H1 p.Ser784= (c.2352C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

DYNC1H1 p.Ser784=

c.2352C>T · rs149028205 · VCV883710

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

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 -5.4	GERP -4.5
Overall
CADD	4.661	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,880 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00149% 24/1,613,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Finnishnot grpmax-eligible	0.00312%	32,006
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,082
European (non-Finnish)	0.000763%	131,111

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.Ser784=
Coding: c.2352C>T
MANE Select: NM_001376
dbSNP: rs149028205
Type: single nucleotide variant
Location: chr14:101986577 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 784: 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: Charcot-Marie-Tooth disease axonal type 2O

Similar variants

DYNC1H1 p.Ser784Asn Uncertain significance ★ same residue
DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/Likely 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.Arg251Ser Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg264Leu 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-ser784 (accessed [today's date]).

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