Is DYNC1H1 p.Ser1503= (c.4509C>T) pathogenic?

DYNC1H1 p.Ser1503= (c.4509C>T) is classified Benign/Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.172%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Ser1503= (c.4509C>T)?

DYNC1H1 p.Ser1503= (c.4509C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease (ClinVar).

How common is DYNC1H1 p.Ser1503= (c.4509C>T) in the general population?

DYNC1H1 p.Ser1503= (c.4509C>T) is rare (popmax 0.172%, afr) (gnomAD).

DYNC1H1 p.Ser1503=

c.4509C>T · rs116089522 · VCV434970

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, afr)

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 -13	GERP -4.6
Overall
CADD	6.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% African / African-American · 129/75,048 alleles

Filtering AF 0.148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.00898% 145/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.172%	582
Remaining individualsnot grpmax-eligible	0.008%	12,502
Admixed American	0.005%	20,010
South Asian	0.0011%	91,084
European (non-Finnish)	0.000593%	168,577

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.Ser1503=
Coding: c.4509C>T
MANE Select: NM_001376
dbSNP: rs116089522
Type: single nucleotide variant
Location: chr14:102001648 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 1503: 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 Charcot-Marie-Tooth disease

Similar variants

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
DYNC1H1 p.Arg292Trp 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-ser1503 (accessed [today's date]).

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