Is DYNC1H1 p.Arg3728Pro (c.11183G>C) pathogenic?

DYNC1H1 p.Arg3728Pro (c.11183G>C) is classified Likely pathogenic in DYNC1H1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-09). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with cortical dysplasia, complex, with other brain malformations 13.

How common is DYNC1H1 p.Arg3728Pro (c.11183G>C) in the general population?

DYNC1H1 p.Arg3728Pro (c.11183G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC1H1 p.Arg3728Pro (c.11183G>C)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Arg3728Pro

Q: What condition is associated with DYNC1H1 p.Arg3728Pro (c.11183G>C)?

DYNC1H1 p.Arg3728Pro (c.11183G>C) is associated with cortical dysplasia, complex, with other brain malformations 13, lissencephaly spectrum disorders (ClinVar).

c.11183G>C · rs797045529 · VCV210861

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cortical dysplasia, complex, with other brain malformations 13

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic ✓ concordant with ClinVar · top 2% in DYNC1H1
REVEL	0.609	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 7,350 bp · p 6.9e-63 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Arg3728Pro
Coding: c.11183G>C
MANE Select: NM_001376
dbSNP: rs797045529
Type: single nucleotide variant
Location: chr14:102038825 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 3728: the 'aaa 5' region; an α-helix

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

Disease context

cortical dysplasia, complex, with other brain malformations 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lissencephaly spectrum disorders

Similar variants

DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Trp 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
DYNC1H1 p.Arg292Trp Pathogenic ★★ same condition
DYNC1H1 p.Arg309His 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-arg3728pro (accessed [today's date]).

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