Is DYNC1H1 p.Ala837= (c.2511A>G) pathogenic?

DYNC1H1 p.Ala837= (c.2511A>G) is classified Benign in DYNC1H1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.88%, sas); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Ala837= (c.2511A>G)?

DYNC1H1 p.Ala837= (c.2511A>G) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease (ClinVar).

How common is DYNC1H1 p.Ala837= (c.2511A>G) in the general population?

DYNC1H1 p.Ala837= (c.2511A>G) is low-frequency (popmax 2.88%, sas) (gnomAD).

DYNC1H1 p.Ala837=

c.2511A>G · rs17512054 · VCV128924

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.88%, sas)

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 -4.9	GERP -4.6
Overall
CADD	1.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.88% South Asian · 2,619/91,088 alleles

Filtering AF 2.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.75%

Overall 1.11% 17,986/1,614,230 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.88%	35
Middle Eastern	1.3%	77
Ashkenazi Jewishnot grpmax-eligible	1.24%	81
European (non-Finnish)	1.12%	89
Remaining individualsnot grpmax-eligible	1.07%	94
Admixed American	0.926%	108
Finnishnot grpmax-eligible	0.548%	182
African / African-American	0.189%	529
Amishnot grpmax-eligible	0.11%	912
East Asian	0.02%	4,988

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.Ala837=
Coding: c.2511A>G
MANE Select: NM_001376
dbSNP: rs17512054
Type: single nucleotide variant
Location: chr14:101986736 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 837: an α-helix; the 'stem' 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: 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-ala837 (accessed [today's date]).

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