Is SKI p.Pro172= (c.516C>T) pathogenic?

SKI p.Pro172= (c.516C>T) is classified Benign/Likely benign in SKI (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-22). Ultra-rare (popmax 0.0723%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is SKI p.Pro172= (c.516C>T) in the general population?

SKI p.Pro172= (c.516C>T) is ultra-rare (popmax 0.0723%, afr) (gnomAD).

SKI p.Pro172=

Q: What condition is associated with SKI p.Pro172= (c.516C>T)?

SKI p.Pro172= (c.516C>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.516C>T · rs182513685 · VCV516445

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0723%, 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 4.7	GERP -3.7, phastCons 1
Overall
CADD	15.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0723% African / African-American · 54/74,656 alleles

Filtering AF 0.0569% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0513%

Overall 0.00495% 79/1,595,498 alleles · ultra-rare exomes 43/1,443,118 · genomes 36/152,380 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0723%	1,383
East Asian	0.0457%	2,188
Remaining individualsnot grpmax-eligible	0.00324%	30,859
European (non-Finnish)	0.000256%	390,605

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.Pro172=
Coding: c.516C>T
MANE Select: NM_003036
dbSNP: rs182513685
Type: single nucleotide variant
Location: chr1:2229282 (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-pro172 (accessed [today's date]).

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