Is DYNC2H1 p.Phe2761fs (c.8283del) pathogenic?

DYNC2H1 p.Phe2761fs (c.8283del) is classified Likely pathogenic in DYNC2H1 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.00267%, afr); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Phe2761fs (c.8283del)?

DYNC2H1 p.Phe2761fs (c.8283del) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Phe2761fs (c.8283del) in the general population?

DYNC2H1 p.Phe2761fs (c.8283del) is very rare (popmax 0.00267%, afr) (gnomAD).

DYNC2H1 p.Phe2761fs

c.8283del · rs1862810311 · VCV873461

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 51 of 89
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,611,712 alleles · very rare exomes 4/1,459,558 · genomes 0/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
Finnishnot grpmax-eligible	0.00157%	63,566
European (non-Finnish)	8.48e-05%	1,178,960

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.Phe2761fs
Coding: c.8283del
MANE Select: NM_001377
dbSNP: rs1862810311
Type: Deletion
Location: chr11:103203742 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2761: the 'aaa 4' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 c.1360+2del Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Arg1881fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Asp4156fs Pathogenic ★★ same condition
DYNC2H1 p.Gln1566fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.His1896fs Pathogenic ★★ same condition
DYNC2H1 p.Ile4057fs Pathogenic ★★ same condition
DYNC2H1 p.Ile452fs Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 p.Leu3370fs 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-phe2761fs (accessed [today's date]).

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