Is DYNC2H1 p.Phe1356= (c.4068C>T) pathogenic?

DYNC2H1 p.Phe1356= (c.4068C>T) is classified Benign/Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 5.77%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Phe1356= (c.4068C>T)?

DYNC2H1 p.Phe1356= (c.4068C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

DYNC2H1 p.Phe1356=

Q: How common is DYNC2H1 p.Phe1356= (c.4068C>T) in the general population?

DYNC2H1 p.Phe1356= (c.4068C>T) is common (popmax 5.77%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4068C>T · rs74713170 · VCV302033

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.77%, afr) — too common for a highly-penetrant pathogenic allele

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 0.46	GERP -2.5, phastCons 1
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.77% African / African-American · 4,325/74,980 alleles

Filtering AF 5.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.57%

Overall 0.327% 5,279/1,613,274 alleles · common exomes 2,694/1,461,044 · genomes 2,585/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.77%	17
Middle Eastern	0.495%	202
Admixed American	0.462%	216
Remaining individualsnot grpmax-eligible	0.418%	239
South Asian	0.0627%	1,595
East Asian	0.058%	1,725
European (non-Finnish)	0.0252%	3,972
Finnishnot grpmax-eligible	0.00938%	10,662

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.Phe1356=
Coding: c.4068C>T
MANE Select: NM_001377
dbSNP: rs74713170
Type: single nucleotide variant
Location: chr11:103156711 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1356: the 'stem' region; 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

Also linked: asphyxiating thoracic dystrophy 3

Similar variants

DYNC2H1 p.Phe1356Leu Uncertain significance ★ ⚠ 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-phe1356 (accessed [today's date]).

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