Is DYNC1H1 p.Ser4480= (c.13440C>T) pathogenic?

DYNC1H1 p.Ser4480= (c.13440C>T) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-20). Rare (popmax 0.324%, afr); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Ser4480= (c.13440C>T)?

DYNC1H1 p.Ser4480= (c.13440C>T) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease (ClinVar).

How common is DYNC1H1 p.Ser4480= (c.13440C>T) in the general population?

DYNC1H1 p.Ser4480= (c.13440C>T) is rare (popmax 0.324%, afr) (gnomAD).

DYNC1H1 p.Ser4480=

c.13440C>T · rs150286673 · VCV210866

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.324%, afr)

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 -20	GERP -4.4
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.324% African / African-American · 243/75,040 alleles

Filtering AF 0.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.277%

Overall 0.0195% 314/1,614,142 alleles · rare exomes 170/1,461,858 · genomes 144/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.324%	309
Admixed American	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0304%	3,290
East Asian	0.0134%	7,479
South Asian	0.00439%	22,769
European (non-Finnish)	0.00127%	78,670

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.Ser4480=
Coding: c.13440C>T
MANE Select: NM_001376
dbSNP: rs150286673
Type: single nucleotide variant
Location: chr14:102049507 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 4480: 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.Ser4480Phe 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-ser4480 (accessed [today's date]).

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