Is SKI p.Glu617= (c.1851G>A) pathogenic?

SKI p.Glu617= (c.1851G>A) is classified Benign/Likely benign in SKI (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-19). Rare (popmax 0.286%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is SKI p.Glu617= (c.1851G>A) in the general population?

SKI p.Glu617= (c.1851G>A) is rare (popmax 0.286%, afr) (gnomAD).

SKI p.Glu617=

Q: What condition is associated with SKI p.Glu617= (c.1851G>A)?

SKI p.Glu617= (c.1851G>A) 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.1851G>A · rs146789646 · VCV198156

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.286%, 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 3.7	GERP 0.72, phastCons 1
Overall
CADD	5.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.286% African / African-American · 214/74,950 alleles

Filtering AF 0.254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.242%

Overall 0.0143% 229/1,600,152 alleles · rare exomes 102/1,447,784 · genomes 127/152,368 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.286%	350
Middle Eastern	0.0166%	6,038
Remaining individualsnot grpmax-eligible	0.0129%	7,758
Admixed American	0.00694%	14,405
South Asian	0.00113%	88,600
European (non-Finnish)	8.51e-05%	1,174,830

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.Glu617=
Coding: c.1851G>A
MANE Select: NM_003036
dbSNP: rs146789646
Type: single nucleotide variant
Location: chr1:2306103 (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

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.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
SKI p.Leu32Val Pathogenic ★★ ⚠ same condition
SKI p.Pro35Ser 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-glu617 (accessed [today's date]).

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