Is DYNC2H1 p.Arg330Cys (c.988C>T) pathogenic?

DYNC2H1 p.Arg330Cys (c.988C>T) is classified Pathogenic/Likely pathogenic in DYNC2H1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.6823); Very rare (popmax 0.00835%, amr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Arg330Cys (c.988C>T)?

DYNC2H1 p.Arg330Cys (c.988C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Arg330Cys (c.988C>T) in the general population?

DYNC2H1 p.Arg330Cys (c.988C>T) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely pathogenic (score 0.6823) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Arg330Cys

c.988C>T · rs397514637 · VCV40070

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.6823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.6823	likely pathogenic ✓ concordant with ClinVar
REVEL	0.641	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	32.0	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

Grpmax group 0.00835% Admixed American · 5/59,872 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.0018% 29/1,610,370 alleles · very rare exomes 26/1,458,132 · genomes 3/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,974
African / African-American	0.00533%	18,751
East Asian	0.00446%	22,413
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,490
Remaining individualsnot grpmax-eligible	0.0016%	62,332
European (non-Finnish)	0.00127%	78,535
South Asian	0.0011%	90,542

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.Arg330Cys
Coding: c.988C>T
MANE Select: NM_001377
dbSNP: rs397514637
Type: single nucleotide variant
Location: chr11:103117852 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 330: the 'stem' region; a UniProt-annotated variant site (in srtd3)

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

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: asphyxiating thoracic dystrophy 3

Similar variants

DYNC2H1 p.Arg330His Likely pathogenic ★ same residue
DYNC2H1 p.Arg330Leu Likely pathogenic ★ same residue
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.10695+1G>A Likely pathogenic ★★ same condition
DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.11493+2T>A 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-arg330cys (accessed [today's date]).

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