Is DYNC2H1 p.Ala384Val (c.1151C>T) pathogenic?

DYNC2H1 p.Ala384Val (c.1151C>T) is classified Pathogenic/Likely pathogenic in DYNC2H1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-05). AlphaMissense: likely pathogenic (0.6726); Ultra-rare (popmax 0.0668%, mid); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ala384Val (c.1151C>T)?

DYNC2H1 p.Ala384Val (c.1151C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Ala384Val (c.1151C>T) in the general population?

DYNC2H1 p.Ala384Val (c.1151C>T) is ultra-rare (popmax 0.0668%, mid) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ala384Val (c.1151C>T)?

AlphaMissense predicts likely pathogenic (score 0.6726) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ala384Val

c.1151C>T · rs369614706 · VCV446677

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.6726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, mid)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.6726	likely pathogenic ✓ concordant with ClinVar
REVEL	0.41	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	29.4	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 0.0668% Middle Eastern · 4/5,988 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00335% 54/1,610,288 alleles · ultra-rare exomes 47/1,458,246 · genomes 7/152,042 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0668%	1,497
South Asian	0.00994%	10,057
Remaining individualsnot grpmax-eligible	0.00963%	10,389
African / African-American	0.00267%	37,434
European (non-Finnish)	0.00263%	38,002
East Asian	0.00224%	44,726
Admixed American	0.00168%	59,648

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.Ala384Val
Coding: c.1151C>T
MANE Select: NM_001377
dbSNP: rs369614706
Type: single nucleotide variant
Location: chr11:103120705 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 384: the 'stem' region

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 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
DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.12156+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-ala384val (accessed [today's date]).

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