Is SKI p.Ala717= (c.2151T>C) pathogenic?

SKI p.Ala717= (c.2151T>C) is classified Likely benign in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-12). Very rare (popmax 0.00281%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with SKI p.Ala717= (c.2151T>C)?

SKI p.Ala717= (c.2151T>C) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is SKI p.Ala717= (c.2151T>C) in the general population?

SKI p.Ala717= (c.2151T>C) is very rare (popmax 0.00281%, afr) (gnomAD).

SKI p.Ala717=

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.2151T>C · rs1640596053 · VCV3223067

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00281%, afr)

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 -4.4	GERP -3.8
Overall
CADD	0.713	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00281% African / African-American · 2/71,092 alleles

Filtering AF 0.000467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000175%

Overall 0.000131% 2/1,532,314 alleles · very rare exomes 2/1,380,174 · genomes 0/152,140 · joint denominator

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: SKI
Protein: p.Ala717=
Coding: c.2151T>C
MANE Select: NM_003036
dbSNP: rs1640596053
Type: single nucleotide variant
Location: chr1:2306729 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB

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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

SKI p.Pro35Ser Pathogenic ★★ ⚠ same condition
SKI p.Thr180Met Pathogenic/Likely pathogenic ★★ same condition
SKI c.1999-3C>T Uncertain significance ★★ same condition
SKI p.Ala208Pro Uncertain significance ★★ ⚠ same condition
SKI p.Ala208Val Uncertain significance ★★ ⚠ same condition
SKI p.Ala298Ser Uncertain significance ★★ ⚠ same condition
SKI p.Ala3Val Uncertain significance ★★ ⚠ same condition
SKI p.Ala416Val 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/ski-p-ala717 (accessed [today's date]).

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