Is SKI p.Lys365= (c.1095G>A) pathogenic?

SKI p.Lys365= (c.1095G>A) is classified Uncertain significance in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). Absent from gnomAD v4.1; Associated with Shprintzen-Goldberg syndrome.

What condition is associated with SKI p.Lys365= (c.1095G>A)?

SKI p.Lys365= (c.1095G>A) is associated with Shprintzen-Goldberg syndrome (ClinVar).

How common is SKI p.Lys365= (c.1095G>A) in the general population?

SKI p.Lys365= (c.1095G>A) is absent from gnomAD v4.1 (gnomAD).

SKI p.Lys365=

c.1095G>A · rs2521472924 · VCV2030741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Shprintzen-Goldberg syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.50	donor gain · deltas
Pangolin	Δ0.56	loss · gain 0.06 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 1.9, phastCons 1
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SKI
Protein: p.Lys365=
Coding: c.1095G>A
MANE Select: NM_003036
dbSNP: rs2521472924
Type: single nucleotide variant
Location: chr1:2303103 (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.Lys365Arg 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
SKI p.Leu32Val 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-lys365 (accessed [today's date]).

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