Is DYNC2H1 p.Lys2887= (c.8661A>G) pathogenic?

DYNC2H1 p.Lys2887= (c.8661A>G) is classified Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-14). Rare (popmax 0.126%, afr); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Lys2887= (c.8661A>G)?

DYNC2H1 p.Lys2887= (c.8661A>G) is associated with asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Lys2887= (c.8661A>G) in the general population?

DYNC2H1 p.Lys2887= (c.8661A>G) is rare (popmax 0.126%, afr) (gnomAD).

DYNC2H1 p.Lys2887=

c.8661A>G · rs376184114 · VCV1579630

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.126%, afr)

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -0.61, phastCons 1
Overall
CADD	5.579	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.126% African / African-American · 92/73,020 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0974%

Overall 0.00631% 97/1,537,708 alleles · rare exomes 34/1,385,534 · genomes 63/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.126%	794
Remaining individualsnot grpmax-eligible	0.00505%	19,801
Admixed American	0.00197%	50,826
South Asian	0.00126%	79,266

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.Lys2887=
Coding: c.8661A>G
MANE Select: NM_001377
dbSNP: rs376184114
Type: single nucleotide variant
Location: chr11:103211910 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2887: an α-helix; the 'stalk' 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

Also linked: Jeune syndrome

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-lys2887 (accessed [today's date]).

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