Is DYNC1H1 p.Ser1824= (c.5472C>T) pathogenic?

DYNC1H1 p.Ser1824= (c.5472C>T) is classified Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0986%, mid); Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Ser1824= (c.5472C>T)?

DYNC1H1 p.Ser1824= (c.5472C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2O, autosomal dominant cerebellar ataxia (ClinVar).

How common is DYNC1H1 p.Ser1824= (c.5472C>T) in the general population?

DYNC1H1 p.Ser1824= (c.5472C>T) is ultra-rare (popmax 0.0986%, mid) (gnomAD).

DYNC1H1 p.Ser1824=

c.5472C>T · rs769577090 · VCV312633

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, mid)

Conditions

Inborn genetic diseases

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 2.1	GERP 1.4, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0986% Middle Eastern · 6/6,084 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00186% 30/1,614,120 alleles · ultra-rare exomes 29/1,461,894 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0986%	1,014
Admixed American	0.0133%	7,500
South Asian	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,936
European (non-Finnish)	0.000424%	236,011

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.Ser1824=
Coding: c.5472C>T
MANE Select: NM_001376
dbSNP: rs769577090
Type: single nucleotide variant
Location: chr14:102005926 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 1824: an α-helix; the 'stem' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2O autosomal dominant cerebellar ataxia

Similar variants

DYNC1H1 p.Ser1824Phe 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-ser1824 (accessed [today's date]).

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