Is DYNC2H1 p.Ser3550= (c.10650A>G) pathogenic?

DYNC2H1 p.Ser3550= (c.10650A>G) is classified Benign/Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.14%, afr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ser3550= (c.10650A>G)?

DYNC2H1 p.Ser3550= (c.10650A>G) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ser3550= (c.10650A>G) in the general population?

DYNC2H1 p.Ser3550= (c.10650A>G) is low-frequency (popmax 1.14%, afr) (gnomAD).

DYNC2H1 p.Ser3550=

c.10650A>G · rs185562630 · VCV281624

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.14%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP -0.57, phastCons 0.93
Overall
CADD	6.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.14% African / African-American · 821/72,208 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0591% 911/1,540,300 alleles · low-frequency exomes 420/1,393,064 · genomes 491/147,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.14%	88
Remaining individualsnot grpmax-eligible	0.077%	1,299
Admixed American	0.0701%	1,426
Middle Eastern	0.017%	5,874
South Asian	0.00248%	40,294
European (non-Finnish)	0.000438%	228,109

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.Ser3550=
Coding: c.10650A>G
MANE Select: NM_001377
dbSNP: rs185562630
Type: single nucleotide variant
Location: chr11:103259932 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3550: an α-helix

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

Similar variants

DYNC2H1 p.Ser3550Pro Pathogenic/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
DYNC2H1 c.11650-1G>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-ser3550 (accessed [today's date]).

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