Is SKI p.Arg219= (c.657C>T) pathogenic?

SKI p.Arg219= (c.657C>T) is classified Likely benign in SKI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-09). No allele count reported in gnomAD v4.1 (AN 1,611,288); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is SKI p.Arg219= (c.657C>T) in the general population?

SKI p.Arg219= (c.657C>T) is no allele count reported in gnomAD v4.1 (AN 1,611,288) (gnomAD).

SKI p.Arg219=

Q: What condition is associated with SKI p.Arg219= (c.657C>T)?

SKI p.Arg219= (c.657C>T) is associated with familial thoracic aortic aneurysm and aortic dissection, Shprintzen-Goldberg syndrome (ClinVar).

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.657C>T · rs2527578925 · VCV1754291

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,288)

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -3.9, phastCons 0.9
Overall
CADD	10.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,288). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SKI
Protein: p.Arg219=
Coding: c.657C>T
MANE Select: NM_003036
dbSNP: rs2527578925
Type: single nucleotide variant
Location: chr1:2229423 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB
Residue 219: a β-strand

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

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Shprintzen-Goldberg syndrome

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

SKI p.Arg219Cys Uncertain significance ★★ ⚠ same residue
SKI p.Arg219His Uncertain significance ★ ⚠ same residue
SKI p.Gly116Glu Pathogenic/Likely pathogenic ★★ same condition
SKI p.Gly117Arg Pathogenic/Likely pathogenic ★★ same condition
SKI p.Gly117Ser Pathogenic/Likely pathogenic ★★ same condition
SKI p.Gly34Cys Pathogenic ★★ ⚠ same condition
SKI p.Gly34Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
SKI p.Gly34Val 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/ski-p-arg219 (accessed [today's date]).

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