Is DYNC1H1 p.Ser3964= (c.11892C>T) pathogenic?

DYNC1H1 p.Ser3964= (c.11892C>T) is classified Likely benign in DYNC1H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). Ultra-rare (popmax 0.0167%, amr); Associated with Charcot-Marie-Tooth disease axonal type 2O.

What condition is associated with DYNC1H1 p.Ser3964= (c.11892C>T)?

DYNC1H1 p.Ser3964= (c.11892C>T) is associated with Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Ser3964= (c.11892C>T) in the general population?

DYNC1H1 p.Ser3964= (c.11892C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

DYNC1H1 p.Ser3964=

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.11892C>T · rs757869882 · VCV718780

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

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 1.1	GERP 1.4, phastCons 1
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,022 alleles

Filtering AF 0.00899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.000619% 10/1,614,226 alleles · ultra-rare exomes 10/1,461,894 · genomes 0/152,332 · joint denominator

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.Ser3964=
Coding: c.11892C>T
MANE Select: NM_001376
dbSNP: rs757869882
Type: single nucleotide variant
Location: chr14:102040624 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

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

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.Ser3964Arg 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-ser3964 (accessed [today's date]).

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