Is DYNC2H1 p.Pro1063Arg (c.3188C>G) pathogenic?

DYNC2H1 p.Pro1063Arg (c.3188C>G) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-31). AlphaMissense: likely pathogenic (0.7123); Ultra-rare (popmax 0.0669%, mid); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Pro1063Arg (c.3188C>G)?

DYNC2H1 p.Pro1063Arg (c.3188C>G) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Pro1063Arg (c.3188C>G) in the general population?

DYNC2H1 p.Pro1063Arg (c.3188C>G) is ultra-rare (popmax 0.0669%, mid) (gnomAD).

What do computational predictors say about DYNC2H1 p.Pro1063Arg (c.3188C>G)?

AlphaMissense predicts likely pathogenic (score 0.7123) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Pro1063Arg

c.3188C>G · rs1287956697 · VCV2441071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7123 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, mid)

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
AlphaMissense	0.7123	likely pathogenic
REVEL	0.385	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.0669% Middle Eastern · 4/5,982 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.000514% 8/1,555,766 alleles · ultra-rare exomes 8/1,403,738 · genomes 0/152,028 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0669%	1,495
European (non-Finnish)	0.000348%	287,308

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: DYNC2H1
Protein: p.Pro1063Arg
Coding: c.3188C>G
MANE Select: NM_001377
dbSNP: rs1287956697
Type: single nucleotide variant
Location: chr11:103153394 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1063: the 'stem' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.12156+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.12457-1G>C Likely pathogenic ★★ same condition
DYNC2H1 c.1662-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.2106+2T>C Likely pathogenic ★★ same condition
DYNC2H1 c.2574+1G>A 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/dync2h1-p-pro1063arg (accessed [today's date]).

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