Is DYNC2H1 p.Ser3073Pro (c.9217T>C) pathogenic?

DYNC2H1 p.Ser3073Pro (c.9217T>C) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-12). AlphaMissense: likely pathogenic (0.905); Ultra-rare (popmax 0.0132%, amr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ser3073Pro (c.9217T>C)?

DYNC2H1 p.Ser3073Pro (c.9217T>C) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Ser3073Pro (c.9217T>C) in the general population?

DYNC2H1 p.Ser3073Pro (c.9217T>C) is ultra-rare (popmax 0.0132%, amr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ser3073Pro (c.9217T>C)?

AlphaMissense predicts likely pathogenic (score 0.905) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ser3073Pro

c.9217T>C · rs199970220 · VCV302078

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, amr)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.905	likely pathogenic
REVEL	0.498	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	26.9	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 0.0132% Admixed American · 7/53,130 alleles

Filtering AF 0.00616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00442%

Overall 0.005% 78/1,560,916 alleles · ultra-rare exomes 71/1,408,614 · genomes 7/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0132%	7,590
European (non-Finnish)	0.00601%	16,652
Remaining individualsnot grpmax-eligible	0.00331%	30,232

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.Ser3073Pro
Coding: c.9217T>C
MANE Select: NM_001377
dbSNP: rs199970220
Type: single nucleotide variant
Location: chr11:103222139 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3073: a turn; the 'stalk' 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-ser3073pro (accessed [today's date]).

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