Is DYNC1H1 p.Ile907= (c.2721T>C) pathogenic?

DYNC1H1 p.Ile907= (c.2721T>C) is classified Benign/Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.71%, afr); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Ile907= (c.2721T>C)?

DYNC1H1 p.Ile907= (c.2721T>C) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O, Charcot-Marie-Tooth disease (ClinVar).

How common is DYNC1H1 p.Ile907= (c.2721T>C) in the general population?

DYNC1H1 p.Ile907= (c.2721T>C) is low-frequency (popmax 1.71%, afr) (gnomAD).

DYNC1H1 p.Ile907=

c.2721T>C · rs114021657 · VCV312625

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.71%, 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	<0.2	all four deltas below 0.2 · T>A here scores Δ0.65 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.47	GERP -1.9, phastCons 0.14
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.71% African / African-American · 1,283/75,030 alleles

Filtering AF 1.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.6%

Overall 0.0906% 1,463/1,614,164 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.71%	58
Remaining individualsnot grpmax-eligible	0.155%	644
Middle Eastern	0.099%	1,010
Admixed American	0.0833%	1,201
South Asian	0.0143%	7,007
European (non-Finnish)	0.00119%	84,288

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.Ile907=
Coding: c.2721T>C
MANE Select: NM_001376
dbSNP: rs114021657
Type: single nucleotide variant
Location: chr14:101988705 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 907: 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.Ile907Met Uncertain significance ★★ same residue
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

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-ile907 (accessed [today's date]).

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