Is DYNC2LI1 p.Tyr336Ter (c.1008C>A) pathogenic?

DYNC2LI1 p.Tyr336Ter (c.1008C>A) is classified Likely pathogenic in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). Very rare (popmax 0.00221%, sas); Associated with short-rib thoracic dysplasia 15 with polydactyly.

What condition is associated with DYNC2LI1 p.Tyr336Ter (c.1008C>A)?

DYNC2LI1 p.Tyr336Ter (c.1008C>A) is associated with short-rib thoracic dysplasia 15 with polydactyly (ClinVar).

How common is DYNC2LI1 p.Tyr336Ter (c.1008C>A) in the general population?

DYNC2LI1 p.Tyr336Ter (c.1008C>A) is very rare (popmax 0.00221%, sas) (gnomAD).

DYNC2LI1 p.Tyr336Ter

c.1008C>A · VCV3629470

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

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	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.57	GERP 1, phastCons 1
Overall
CADD	38.0	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 0.00221% South Asian · 2/90,698 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,459,496 alleles · very rare

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.Tyr336Ter
Coding: c.1008C>A
MANE Select: NM_022436 · reported on NM_016008
Type: single nucleotide variant
Location: chr2:43809719 (GRCh38)

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

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-tyr336ter (accessed [today's date]).

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