Is DYNC1H1 p.Pro3647= (c.10941G>A) pathogenic?

DYNC1H1 p.Pro3647= (c.10941G>A) is classified Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-10). Ultra-rare (popmax 0.0165%, mid); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Pro3647= (c.10941G>A)?

DYNC1H1 p.Pro3647= (c.10941G>A) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease (ClinVar).

How common is DYNC1H1 p.Pro3647= (c.10941G>A) in the general population?

DYNC1H1 p.Pro3647= (c.10941G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

DYNC1H1 p.Pro3647=

c.10941G>A · rs374214760 · VCV514404

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, 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 -9.3	GERP -4.6
Overall
CADD	0.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.0044% 71/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
Admixed American	0.00834%	11,998
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00475%	21,072
South Asian	0.00329%	30,361
African / African-American	0.00267%	37,457

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.Pro3647=
Coding: c.10941G>A
MANE Select: NM_001376
dbSNP: rs374214760
Type: single nucleotide variant
Location: chr14:102038492 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 3647: the 'aaa 5' region; an α-helix

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 Charcot-Marie-Tooth disease

Similar variants

DYNC1H1 p.Pro3647Ala Uncertain significance ★★ same residue
DYNC1H1 p.Pro3647Leu Uncertain significance ★ ⚠ same residue
DYNC1H1 p.Pro3647Ser 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

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-pro3647 (accessed [today's date]).

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