Is DYNC1H1 p.Pro4037Phe (c.12109_12110delinsTT) pathogenic?

DYNC1H1 p.Pro4037Phe (c.1210912110delinsTT) is classified Uncertain significance in DYNC1H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-06). Absent from gnomAD; Associated with Charcot-Marie-Tooth disease axonal type 2O.

What condition is associated with DYNC1H1 p.Pro4037Phe (c.12109_12110delinsTT)?

DYNC1H1 p.Pro4037Phe (c.12109_12110delinsTT) is associated with Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Pro4037Phe (c.12109_12110delinsTT) in the general population?

DYNC1H1 p.Pro4037Phe (c.12109_12110delinsTT) is absent from gnomAD (gnomAD).

DYNC1H1 p.Pro4037Phe

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2O inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.12109_12110delinsTT · rs1595631704 · VCV658365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease axonal type 2O

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 3,012 bp · p 1.6e-29 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DYNC1H1
Protein: p.Pro4037Phe
Coding: c.12109_12110delinsTT
MANE Select: NM_001376
dbSNP: rs1595631704
Type: Indel
Location: chr14:102042019 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 4037: the 'aaa 6' region; a β-strand

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

Disease context

Charcot-Marie-Tooth disease axonal type 2O — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant Charcot-Marie-Tooth disease type 2O (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

DYNC1H1 p.Gln2928Leu Uncertain significance ★★ same condition
DYNC1H1 p.Lys4601Ala Uncertain significance ★★ same condition
DYNC1H1 c.3015+17_3015+18delinsCT Likely pathogenic ★ same condition
DYNC1H1 c.13372+8_13372+9delinsGA Uncertain significance ★ same condition
DYNC1H1 c.4074+4_4074+5delinsAT Uncertain significance ★ same condition
DYNC1H1 p.Ala25Lys Uncertain significance ★ same condition
DYNC1H1 p.Ile209Val Uncertain significance ★ same condition
DYNC1H1 p.Leu2295Gly Uncertain significance ★ 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-pro4037phe (accessed [today's date]).

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