Is DYNC2I1 p.Arg762Ter (c.2284C>T) pathogenic?

DYNC2I1 p.Arg762Ter (c.2284C>T) is classified Pathogenic in DYNC2I1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-23). Very rare (popmax 0.00223%, eas); Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

How common is DYNC2I1 p.Arg762Ter (c.2284C>T) in the general population?

DYNC2I1 p.Arg762Ter (c.2284C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

DYNC2I1 p.Arg762Ter

Q: What condition is associated with DYNC2I1 p.Arg762Ter (c.2284C>T)?

DYNC2I1 p.Arg762Ter (c.2284C>T) is associated with short-rib thoracic dysplasia 8 with or without polydactyly, asphyxiating thoracic dystrophy 3 (ClinVar).

c.2284C>T · rs1456300819 · VCV446629

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

short-rib thoracic dysplasia 8 with or without 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	predicted	premature termination codon in exon 18 of 25
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4	GERP -3.7
Overall
CADD	35.0	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 0.00223% East Asian · 1/44,892 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,613,284 alleles · very rare exomes 6/1,461,124 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
Admixed American	0.00167%	59,936
African / African-American	0.00133%	74,910
European (non-Finnish)	0.000509%	196,617

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: DYNC2I1
Protein: p.Arg762Ter
Coding: c.2284C>T
MANE Select: NM_018051
dbSNP: rs1456300819
Type: single nucleotide variant
Location: chr7:158926213 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.87 · 4 PDB
Residue 762: a UniProt-annotated variant site (in srtd8; reduces interaction with ift proteins); a UniProt-annotated variant site (in srtd8)

Full DYNC2I1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 8 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: asphyxiating thoracic dystrophy 3

Similar variants

DYNC2I1 p.Arg762Gln Uncertain significance ★ ⚠ same residue
DYNC2I1 p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg441Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg642Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala609Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala800Thr Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala822Thr 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/dync2i1-p-arg762ter (accessed [today's date]).

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