Is DYNC1H1 p.Arg2332Cys (c.6994C>T) pathogenic?

DYNC1H1 p.Arg2332Cys (c.6994C>T) is classified Pathogenic/Likely pathogenic in DYNC1H1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.9909); Absent from gnomAD v4.1; Associated with DYNC1H1-related disorder.

What condition is associated with DYNC1H1 p.Arg2332Cys (c.6994C>T)?

DYNC1H1 p.Arg2332Cys (c.6994C>T) is associated with DYNC1H1-related disorder, microcephaly, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Arg2332Cys (c.6994C>T) in the general population?

DYNC1H1 p.Arg2332Cys (c.6994C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC1H1 p.Arg2332Cys (c.6994C>T)?

AlphaMissense predicts likely pathogenic (score 0.9909) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Arg2332Cys

c.6994C>T · rs1057518961 · VCV374190

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9909 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

DYNC1H1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9909	likely pathogenic ✓ concordant with ClinVar
REVEL	0.946	strongly 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 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 3,245 bp · p 4.2e-21 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYNC1H1
Protein: p.Arg2332Cys
Coding: c.6994C>T
MANE Select: NM_001376
dbSNP: rs1057518961
Type: single nucleotide variant
Location: chr14:102012450 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 2332: a β-strand; the 'aaa 2' region

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

Disease context

Also linked: microcephaly Charcot-Marie-Tooth disease axonal type 2O cortical dysplasia, complex, with other brain malformations 13

Similar variants

DYNC1H1 p.Arg2332Gly Likely pathogenic ★ same residue
DYNC1H1 p.Arg2332Leu Likely pathogenic ★ same residue
DYNC1H1 p.Arg2332= Likely benign ★ same residue
DYNC1H1 p.Arg2332His Pathogenic/Likely pathogenic ★★ same residue
DYNC1H1 c.4396-1G>C Likely pathogenic ★★ same condition
DYNC1H1 p.Ala4519Val Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/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-arg2332cys (accessed [today's date]).

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