Is DYNC2H1 p.His748= (c.2244C>T) pathogenic?

DYNC2H1 p.His748= (c.2244C>T) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-03). Rare (popmax 0.181%, sas); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.His748= (c.2244C>T)?

DYNC2H1 p.His748= (c.2244C>T) is associated with Jeune syndrome, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.His748= (c.2244C>T) in the general population?

DYNC2H1 p.His748= (c.2244C>T) is rare (popmax 0.181%, sas) (gnomAD).

DYNC2H1 p.His748=

c.2244C>T · rs373707570 · VCV302016

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.181%, sas)

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 1.1	GERP 2.4, phastCons 1
Overall
CADD	7.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% South Asian · 158/87,360 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.0167% 268/1,601,966 alleles · rare exomes 197/1,449,726 · genomes 71/152,240 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.181%	553
African / African-American	0.133%	754
Remaining individualsnot grpmax-eligible	0.0145%	6,890
Admixed American	0.00346%	28,933

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.His748=
Coding: c.2244C>T
MANE Select: NM_001377
dbSNP: rs373707570
Type: single nucleotide variant
Location: chr11:103135533 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 748: 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-his748 (accessed [today's date]).

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