Is DYNC1H1 p.Arg3611= (c.10833G>C) pathogenic?

DYNC1H1 p.Arg3611= (c.10833G>C) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-12-28). Ultra-rare (popmax 0.0822%, mid); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Arg3611= (c.10833G>C)?

DYNC1H1 p.Arg3611= (c.10833G>C) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Arg3611= (c.10833G>C) in the general population?

DYNC1H1 p.Arg3611= (c.10833G>C) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

DYNC1H1 p.Arg3611=

c.10833G>C · rs35143882 · VCV510280

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Conditions

autosomal dominant cerebellar ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -4.6, phastCons 1
Overall
CADD	13.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00366% 59/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
South Asian	0.0297%	3,373
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00178%	56,191
Admixed American	0.00167%	60,000

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.Arg3611=
Coding: c.10833G>C
MANE Select: NM_001376
dbSNP: rs35143882
Type: single nucleotide variant
Location: chr14:102036567 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 3611: the 'aaa 5' region; a β-strand

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.Arg3611Gln Conflicting classifications of pathogenicity ★ same residue
DYNC1H1 p.Arg3611Pro 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

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-arg3611 (accessed [today's date]).

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