Is DYNC1H1 p.Ser3355= (c.10065T>C) pathogenic?

DYNC1H1 p.Ser3355= (c.10065T>C) is classified Benign/Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-06-01). Rare (popmax 0.176%, nfe); Associated with Charcot-Marie-Tooth disease axonal type 2O.

How common is DYNC1H1 p.Ser3355= (c.10065T>C) in the general population?

DYNC1H1 p.Ser3355= (c.10065T>C) is rare (popmax 0.176%, nfe) (gnomAD).

DYNC1H1 p.Ser3355=

Q: What condition is associated with DYNC1H1 p.Ser3355= (c.10065T>C)?

DYNC1H1 p.Ser3355= (c.10065T>C) is associated with Charcot-Marie-Tooth disease axonal type 2O, autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures, cortical dysplasia, complex, with other brain malformations 13 (ClinVar).

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2O inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.10065T>C · rs80096622 · VCV238992

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

rare (popmax 0.176%, nfe)

Conditions

Charcot-Marie-Tooth disease axonal type 2O

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 -20	GERP -4.6
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.176% European (non-Finnish) · 2,077/1,180,038 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.149% 2,411/1,614,134 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.176%	568
Remaining individualsnot grpmax-eligible	0.157%	638
South Asian	0.15%	665
Middle Eastern	0.148%	674
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
Finnishnot grpmax-eligible	0.0547%	1,828
Admixed American	0.0417%	2,400
African / African-American	0.0173%	5,773

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.Ser3355=
Coding: c.10065T>C
MANE Select: NM_001376
dbSNP: rs80096622
Type: single nucleotide variant
Location: chr14:102032453 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 3355: the 'stalk' region

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

Disease context

Charcot-Marie-Tooth disease axonal type 2O — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Autosomal dominant Charcot-Marie-Tooth disease type 2O (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

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
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-ser3355 (accessed [today's date]).

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