Is DYNC1H1 p.Pro208= (c.624G>A) pathogenic?

DYNC1H1 p.Pro208= (c.624G>A) is classified Benign in DYNC1H1 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). Common (popmax 49.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant cerebellar ataxia.

DYNC1H1 p.Pro208=

Q: What condition is associated with DYNC1H1 p.Pro208= (c.624G>A)?

DYNC1H1 p.Pro208= (c.624G>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).

Q: How common is DYNC1H1 p.Pro208= (c.624G>A) in the general population?

DYNC1H1 p.Pro208= (c.624G>A) is common (popmax 49.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.624G>A · rs3818188 · VCV128939

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Common

common (popmax 49.3%, eas) — too common for a highly-penetrant pathogenic allele

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 -5	GERP -4.6
Overall
CADD	4.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 49.3% East Asian · 22,107/44,868 alleles

Filtering AF 48.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.5%

Overall 19.1% 307,852/1,614,016 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	49.3%	2
Admixed American	33.9%	3
Amishnot grpmax-eligible	31.6%	3
Ashkenazi Jewishnot grpmax-eligible	29.3%	3
Remaining individualsnot grpmax-eligible	20.3%	5
Middle Eastern	20%	5
Finnishnot grpmax-eligible	19.7%	5
European (non-Finnish)	18.2%	6
South Asian	14%	7
African / African-American	4.06%	25

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.Pro208=
Coding: c.624G>A
MANE Select: NM_001376
dbSNP: rs3818188
Type: single nucleotide variant
Location: chr14:101979824 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 208: the 'stem' region; an α-helix

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.Pro208Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro208 (accessed [today's date]).

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