Is DYNC2I2 p.Tyr180= (c.540C>T) pathogenic?

DYNC2I2 p.Tyr180= (c.540C>T) is classified Likely benign in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). Ultra-rare (popmax 0.0593%, sas); Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Tyr180= (c.540C>T)?

DYNC2I2 p.Tyr180= (c.540C>T) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

How common is DYNC2I2 p.Tyr180= (c.540C>T) in the general population?

DYNC2I2 p.Tyr180= (c.540C>T) is ultra-rare (popmax 0.0593%, sas) (gnomAD).

DYNC2I2 p.Tyr180=

c.540C>T · rs542055273 · VCV761421

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0593%, sas)

Conditions

short-rib thoracic dysplasia 11 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.9	GERP -3.1
Overall
CADD	5.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0593% South Asian · 54/90,994 alleles

Filtering AF 0.0467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.00552% 89/1,611,192 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0593%	1,685
Admixed American	0.015%	6,661
Remaining individualsnot grpmax-eligible	0.00641%	15,611
African / African-American	0.00267%	37,521
European (non-Finnish)	0.00161%	62,055
Finnishnot grpmax-eligible	0.00161%	62,302

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: DYNC2I2
Protein: p.Tyr180=
Coding: c.540C>T
MANE Select: NM_052844
dbSNP: rs542055273
Type: single nucleotide variant
Location: chr9:128636923 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB

Full DYNC2I2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 11 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Arg121Ter Pathogenic ★★ same condition
DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
DYNC2I2 p.Arg447Trp Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Ala131Val Uncertain significance ★★ ⚠ same condition
DYNC2I2 p.Ala13Gly Uncertain significance ★★ ⚠ same condition
DYNC2I2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
DYNC2I2 p.Ala369Val 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/dync2i2-p-tyr180 (accessed [today's date]).

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