Is DYNC2I2 p.Pro210Arg (c.629C>G) pathogenic?

DYNC2I2 p.Pro210Arg (c.629C>G) is classified Uncertain significance in DYNC2I2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.8653); Very rare (popmax 0.00204%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYNC2I2 p.Pro210Arg (c.629C>G)?

DYNC2I2 p.Pro210Arg (c.629C>G) is associated with Inborn genetic diseases, short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Pro210Arg (c.629C>G) in the general population?

DYNC2I2 p.Pro210Arg (c.629C>G) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about DYNC2I2 p.Pro210Arg (c.629C>G)?

AlphaMissense predicts likely pathogenic (score 0.8653) — an in-silico prediction, not a clinical call.

DYNC2I2 p.Pro210Arg

c.629C>G · rs780689247 · VCV2151035

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8653	likely pathogenic · top 8% in DYNC2I2
REVEL	0.651	pathogenic-leaning
SaProt	LLR -18.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.59 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00204% European (non-Finnish) · 24/1,177,702 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,608,166 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	49,071
Remaining individualsnot grpmax-eligible	0.00161%	62,188

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: DYNC2I2
Protein: p.Pro210Arg
Coding: c.629C>G
MANE Select: NM_052844
dbSNP: rs780689247
Type: single nucleotide variant
Location: chr9:128636355 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB

Full DYNC2I2 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: short-rib thoracic dysplasia 11 with or without polydactyly

Similar variants

DYNC2I2 p.Pro210= Benign ★★ same residue
DYNC2I2 p.Pro210Leu Uncertain significance ★ ⚠ same residue
DYNC2I2 p.Pro210fs Pathogenic/Likely pathogenic ★★ same residue
DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Arg121Ter Pathogenic ★★ same condition
DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
DYNC2I2 p.Arg447Trp Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Ala131Val Uncertain significance ★★ ⚠ 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/dync2i2-p-pro210arg (accessed [today's date]).

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