Is DYNC2LI1 p.Trp7fs (c.18_19del) pathogenic?

DYNC2LI1 p.Trp7fs (c.1819del) is classified Pathogenic in DYNC2LI1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-20). Very rare (popmax 0.0018%, amr); Associated with short-rib thoracic dysplasia 15 with polydactyly.

What condition is associated with DYNC2LI1 p.Trp7fs (c.18_19del)?

DYNC2LI1 p.Trp7fs (c.18_19del) is associated with short-rib thoracic dysplasia 15 with polydactyly (ClinVar).

How common is DYNC2LI1 p.Trp7fs (c.18_19del) in the general population?

DYNC2LI1 p.Trp7fs (c.18_19del) is very rare (popmax 0.0018%, amr) (gnomAD).

DYNC2LI1 p.Trp7fs

c.18_19del · rs1435689952 · VCV1106719

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0018%, amr)

Conditions

short-rib thoracic dysplasia 15 with polydactyly

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 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.1	GERP 2, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0018% Admixed American · 1/55,458 alleles

Filtering AF 0.000784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000622%

Overall 0.00115% 18/1,562,094 alleles · very rare exomes 17/1,409,958 · genomes 1/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0018%	55,458
Remaining individualsnot grpmax-eligible	0.00166%	60,080
European (non-Finnish)	0.00131%	76,591
South Asian	0.00119%	83,852

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: DYNC2LI1
Protein: p.Trp7fs
Coding: c.18_19del
MANE Select: NM_016008
dbSNP: rs1435689952
Type: Microsatellite
Location: chr2:43776787 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 3 PDB

Full DYNC2LI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 15 with polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2LI1 p.Leu117Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
DYNC2LI1 p.Trp124Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2LI1 p.Leu6Phe Likely benign ★★ ⚠ same condition
DYNC2LI1 p.Phe33Ser Benign ★★ same condition
DYNC2LI1 c.993+1G>A Pathogenic ★ same condition
DYNC2LI1 p.Arg207Ter Pathogenic ★ same condition
DYNC2LI1 p.Lys140_Val141insTer Pathogenic ★ same condition
DYNC2LI1 p.Met1Thr 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/dync2li1-p-trp7fs (accessed [today's date]).

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