Is SKI p.Pro87Ser (c.259C>T) pathogenic?

SKI p.Pro87Ser (c.259C>T) is classified Uncertain significance in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely benign (0.1205); No allele count reported in gnomAD v4.1 (AN 1,597,030).

How common is SKI p.Pro87Ser (c.259C>T) in the general population?

SKI p.Pro87Ser (c.259C>T) is no allele count reported in gnomAD v4.1 (AN 1,597,030) (gnomAD).

What do computational predictors say about SKI p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

SKI p.Pro87Ser

c.259C>T · rs2527576755 · VCV3027309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,597,030)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
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	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,597,030). 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.Pro87Ser
Coding: c.259C>T
MANE Select: NM_003036
dbSNP: rs2527576755
Type: single nucleotide variant
Location: chr1:2229025 (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.Pro87Arg Uncertain significance ★ same residue
SKI p.Pro87= 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-pro87ser (accessed [today's date]).

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