Is DYNC1H1 p.Pro2020Ala (c.6058C>G) pathogenic?

DYNC1H1 p.Pro2020Ala (c.6058C>G) is classified Uncertain significance in DYNC1H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.9796); Absent from gnomAD v4.1; Associated with cortical dysplasia, complex, with other brain malformations 13.

What condition is associated with DYNC1H1 p.Pro2020Ala (c.6058C>G)?

DYNC1H1 p.Pro2020Ala (c.6058C>G) is associated with cortical dysplasia, complex, with other brain malformations 13 (ClinVar).

How common is DYNC1H1 p.Pro2020Ala (c.6058C>G) in the general population?

DYNC1H1 p.Pro2020Ala (c.6058C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC1H1 p.Pro2020Ala (c.6058C>G)?

AlphaMissense predicts likely pathogenic (score 0.9796) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Pro2020Ala

c.6058C>G · rs2503750846 · VCV1709387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9796 · 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	0.9796	likely pathogenic
REVEL	0.599	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 385 bp · p 6.1e-14 · regional, not allelic
Overall
CADD	24.6	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.Pro2020Ala
Coding: c.6058C>G
MANE Select: NM_001376
dbSNP: rs2503750846
Type: single nucleotide variant
Location: chr14:102009923 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 2020: the 'aaa 1' region

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

Similar variants

DYNC1H1 p.Pro2020Ser Pathogenic ★ 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.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

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-pro2020ala (accessed [today's date]).

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