Is SKI p.Pro89Arg (c.266C>G) pathogenic?

SKI p.Pro89Arg (c.266C>G) is classified Uncertain significance in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-05). AlphaMissense: likely pathogenic (0.8638); Absent from gnomAD v4.1.

How common is SKI p.Pro89Arg (c.266C>G) in the general population?

SKI p.Pro89Arg (c.266C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SKI p.Pro89Arg (c.266C>G)?

AlphaMissense predicts likely pathogenic (score 0.8638) — an in-silico prediction, not a clinical call.

SKI p.Pro89Arg

c.266C>G · rs2100789913 · VCV1302257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8638	likely pathogenic
REVEL	0.759	pathogenic-leaning
SaProt	LLR -10.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 289 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro89Arg
Coding: c.266C>G
MANE Select: NM_003036
dbSNP: rs2100789913
Type: single nucleotide variant
Location: chr1:2229032 (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

Similar variants

SKI p.Pro89Ser Pathogenic ★★ ⚠ same residue
SKI p.Pro89= Likely benign ★★ same residue
SKI p.Gly116Glu Pathogenic/Likely pathogenic ★★ same type
SKI p.Gly117Arg Pathogenic/Likely pathogenic ★★ same type
SKI p.Gly117Ser Pathogenic/Likely pathogenic ★★ same type
SKI p.Gly34Cys Pathogenic ★★ ⚠ same type
SKI p.Gly34Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
SKI p.Gly34Val Pathogenic ★★ ⚠ 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-pro89arg (accessed [today's date]).

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