Is DYNC1H1 p.Leu2379= (c.7137G>A) pathogenic?

DYNC1H1 p.Leu2379= (c.7137G>A) is classified Benign/Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-01-26). Low-frequency (popmax 2.98%, afr); Associated with autosomal dominant cerebellar ataxia.

How common is DYNC1H1 p.Leu2379= (c.7137G>A) in the general population?

DYNC1H1 p.Leu2379= (c.7137G>A) is low-frequency (popmax 2.98%, afr) (gnomAD).

DYNC1H1 p.Leu2379=

Q: What condition is associated with DYNC1H1 p.Leu2379= (c.7137G>A)?

DYNC1H1 p.Leu2379= (c.7137G>A) is associated with autosomal dominant cerebellar ataxia, autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

c.7137G>A · rs17512439 · VCV128940

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.98%, 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 6.7	GERP 1.1, phastCons 1
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.98% African / African-American · 2,240/75,046 alleles

Filtering AF 2.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.84%

Overall 0.16% 2,575/1,614,210 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.98%	34
Admixed American	0.25%	400
Remaining individualsnot grpmax-eligible	0.173%	579
Middle Eastern	0.115%	866
South Asian	0.00768%	13,013
European (non-Finnish)	0.00517%	19,345
East Asian	0.00446%	22,442

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.Leu2379=
Coding: c.7137G>A
MANE Select: NM_001376
dbSNP: rs17512439
Type: single nucleotide variant
Location: chr14:102015227 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 2379: an α-helix; the 'aaa 2' region

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: autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures Charcot-Marie-Tooth disease axonal type 2O cortical dysplasia, complex, with other brain malformations 13 Charcot-Marie-Tooth disease

Similar variants

DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Trp 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.Arg2492Ter Likely pathogenic ★★ same condition
DYNC1H1 p.Arg251Ser Pathogenic/Likely 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-leu2379 (accessed [today's date]).

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