Is DYNC1H1 p.Phe4624= (c.13872C>T) pathogenic?

DYNC1H1 p.Phe4624= (c.13872C>T) is classified Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-17). Ultra-rare (popmax 0.0495%, mid); Associated with Charcot-Marie-Tooth disease axonal type 2O.

What condition is associated with DYNC1H1 p.Phe4624= (c.13872C>T)?

DYNC1H1 p.Phe4624= (c.13872C>T) is associated with Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Phe4624= (c.13872C>T) in the general population?

DYNC1H1 p.Phe4624= (c.13872C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

DYNC1H1 p.Phe4624=

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.13872C>T · rs375918532 · VCV1531529

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -4.2
Overall
CADD	1.815	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00229% 37/1,614,208 alleles · ultra-rare exomes 34/1,461,894 · genomes 3/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
South Asian	0.0143%	7,007
East Asian	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00167%	60,010
African / African-American	0.00133%	75,052
European (non-Finnish)	0.00102%	98,337

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.Phe4624=
Coding: c.13872C>T
MANE Select: NM_001376
dbSNP: rs375918532
Type: single nucleotide variant
Location: chr14:102050494 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 4624: 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.Phe4624Leu 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-phe4624 (accessed [today's date]).

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