Is DYNC1H1 p.Phe1093Ser (c.3278T>C) pathogenic?

DYNC1H1 p.Phe1093Ser (c.3278T>C) is classified Pathogenic in DYNC1H1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-06). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Phe1093Ser (c.3278T>C)?

DYNC1H1 p.Phe1093Ser (c.3278T>C) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2O, cortical dysplasia, complex, with other brain malformations 13 (ClinVar).

How common is DYNC1H1 p.Phe1093Ser (c.3278T>C) in the general population?

DYNC1H1 p.Phe1093Ser (c.3278T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC1H1 p.Phe1093Ser (c.3278T>C)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Phe1093Ser

c.3278T>C · rs1555408829 · VCV449962

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,242)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic ✓ concordant with ClinVar · top 6% in DYNC1H1
REVEL	0.824	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 8,162 bp · p 7.9e-20 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,242). 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.Phe1093Ser
Coding: c.3278T>C
MANE Select: NM_001376
dbSNP: rs1555408829
Type: single nucleotide variant
Location: chr14:101994794 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 1093: a β-strand; the 'stem' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2O cortical dysplasia, complex, with other brain malformations 13 autosomal dominant childhood-onset proximal spinal muscular atrophy

Similar variants

DYNC1H1 p.Phe1093Leu Uncertain significance ★ 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-phe1093ser (accessed [today's date]).

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