Is SKI p.Ser278fs (c.832dup) pathogenic?

SKI p.Ser278fs (c.832dup) is classified Likely pathogenic in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-21). Associated with neurodevelopmental disorder.

What condition is associated with SKI p.Ser278fs (c.832dup)?

SKI p.Ser278fs (c.832dup) is associated with neurodevelopmental disorder (ClinVar).

SKI p.Ser278fs

c.832dup · VCV3376870

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP -4.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: SKI
Protein: p.Ser278fs
Coding: c.832dup
MANE Select: NM_003036
Type: Duplication
Location: chr1:2229597 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB
Residue 278: an α-helix

Full SKI gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SKI p.Ser278Ter Uncertain significance ★★ same residue
SKI p.Gln342fs Likely pathogenic ★ same condition
SKI p.Arg380Ter Uncertain significance ★ same condition
SKI p.Arg319fs Pathogenic ★ same type
SKI p.Ala345fs Uncertain significance ★ same type
SKI p.Ala59_Val60insAlaAla Uncertain significance ★ same type
SKI p.Ala717_Ter729= Uncertain significance ★ same type
SKI p.Ala718_Ter729= Uncertain significance ★ same type

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-ser278fs (accessed [today's date]).

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