Is DYNC1H1 p.Gln391= (c.1173A>G) pathogenic?

DYNC1H1 p.Gln391= (c.1173A>G) is classified Benign/Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Rare (popmax 0.148%, mid); Associated with Charcot-Marie-Tooth disease.

What condition is associated with DYNC1H1 p.Gln391= (c.1173A>G)?

DYNC1H1 p.Gln391= (c.1173A>G) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Gln391= (c.1173A>G) in the general population?

DYNC1H1 p.Gln391= (c.1173A>G) is rare (popmax 0.148%, mid) (gnomAD).

DYNC1H1 p.Gln391=

c.1173A>G · rs17540735 · VCV385969

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Conditions

Charcot-Marie-Tooth disease

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 0.2	GERP -3.4, phastCons 0.001
Overall
CADD	7.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0856% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.078%

Overall 0.0268% 432/1,614,248 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
Admixed American	0.107%	938
African / African-American	0.0826%	1,211
Remaining individualsnot grpmax-eligible	0.0608%	1,645
European (non-Finnish)	0.0216%	4,628
East Asian	0.00223%	44,886
South Asian	0.0022%	45,542
Finnishnot grpmax-eligible	0.00156%	64,048

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.Gln391=
Coding: c.1173A>G
MANE Select: NM_001376
dbSNP: rs17540735
Type: single nucleotide variant
Location: chr14:101983230 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 391: an α-helix; the 'stem' region

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

Disease context

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

Also linked: Charcot-Marie-Tooth disease axonal type 2O

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-gln391 (accessed [today's date]).

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