Is DYNC2LI1 p.Trp124Ter (c.372G>A) pathogenic?

DYNC2LI1 p.Trp124Ter (c.372G>A) is classified Pathogenic/Likely pathogenic in DYNC2LI1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-04). Ultra-rare (popmax 0.0108%, nfe); Associated with asphyxiating thoracic dystrophy 1.

What condition is associated with DYNC2LI1 p.Trp124Ter (c.372G>A)?

DYNC2LI1 p.Trp124Ter (c.372G>A) is associated with asphyxiating thoracic dystrophy 1, short-rib thoracic dysplasia 15 with polydactyly (ClinVar).

How common is DYNC2LI1 p.Trp124Ter (c.372G>A) in the general population?

DYNC2LI1 p.Trp124Ter (c.372G>A) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

DYNC2LI1 p.Trp124Ter

c.372G>A · rs769975073 · VCV212766

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Conditions

asphyxiating thoracic dystrophy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 13
REVEL	0.328	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Overall
CADD	44.0	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 0.0108% European (non-Finnish) · 128/1,179,916 alleles

Filtering AF 0.00928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00872%

Overall 0.00812% 131/1,613,620 alleles · ultra-rare exomes 130/1,461,644 · genomes 1/151,976 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,218
Remaining individualsnot grpmax-eligible	0.0032%	31,235
Finnishnot grpmax-eligible	0.00156%	63,928

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.Trp124Ter
Coding: c.372G>A
MANE Select: NM_016008
dbSNP: rs769975073
Type: single nucleotide variant
Location: chr2:43794508 (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

asphyxiating thoracic dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 15 with polydactyly

Similar variants

DYNC2LI1 p.Leu117Val 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.Met1Thr Pathogenic ★ same condition
DYNC2LI1 p.Thr220Ile Pathogenic ★ ⚠ same condition
DYNC2LI1 c.127-8A>G Uncertain significance ★ 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-trp124ter (accessed [today's date]).

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