Is SKI p.Ala66Pro (c.195_196delinsAC) pathogenic?

SKI p.Ala66Pro (c.195196delinsAC) is classified Uncertain significance in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-09). No gnomAD frequency available for this variant; Associated with Shprintzen-Goldberg syndrome.

What condition is associated with SKI p.Ala66Pro (c.195_196delinsAC)?

SKI p.Ala66Pro (c.195_196delinsAC) is associated with Shprintzen-Goldberg syndrome (ClinVar).

How common is SKI p.Ala66Pro (c.195_196delinsAC) in the general population?

SKI p.Ala66Pro (c.195_196delinsAC) is no gnomAD frequency available for this variant (gnomAD).

SKI p.Ala66Pro

c.195_196delinsAC · rs2527576254 · VCV2741303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Shprintzen-Goldberg syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.14	GERP -1, phastCons 0.95
Regional constraint	o/e 1.14	unconstrained · MANE · 253 bp · p 0.099 · regional, not allelic
Region caveats
Repeat context	tandem	(CGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala66Pro
Coding: c.195_196delinsAC
MANE Select: NM_003036
dbSNP: rs2527576254
Type: Indel
Location: chr1:2228961 (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

Shprintzen-Goldberg syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SKI p.Ala66Thr Uncertain significance ★★ ⚠ same residue
SKI p.Ala67Asn Uncertain significance ★ same condition
SKI p.Val439Phe Uncertain significance ★ same condition
SKI p.Val64Ser Uncertain significance ★ same condition
SKI p.Ala66= Likely benign ★ same residue
SKI p.Glu704_Leu705= Likely benign ★ same condition
SKI p.Ser135_Leu136= Likely benign ★ same condition
SKI p.Gly116Glu Pathogenic/Likely 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-ala66pro (accessed [today's date]).

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