Is SKI p.Ser31Pro (c.91T>C) pathogenic?

SKI p.Ser31Pro (c.91T>C) is classified Pathogenic in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-29). AlphaMissense: likely pathogenic (0.9968); No allele count reported in gnomAD v4.1 (AN 1,427,738); Associated with Shprintzen-Goldberg syndrome.

What condition is associated with SKI p.Ser31Pro (c.91T>C)?

SKI p.Ser31Pro (c.91T>C) is associated with Shprintzen-Goldberg syndrome (ClinVar).

How common is SKI p.Ser31Pro (c.91T>C) in the general population?

SKI p.Ser31Pro (c.91T>C) is no allele count reported in gnomAD v4.1 (AN 1,427,738) (gnomAD).

What do computational predictors say about SKI p.Ser31Pro (c.91T>C)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

SKI p.Ser31Pro

c.91T>C · rs1569656981 · VCV692060

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,427,738)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Shprintzen-Goldberg syndrome

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic ✓ concordant with ClinVar · top 8% in SKI
REVEL	0.53	indeterminate
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 253 bp · p 0.099 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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 1,427,738). 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.Ser31Pro
Coding: c.91T>C
MANE Select: NM_003036
dbSNP: rs1569656981
Type: single nucleotide variant
Location: chr1:2228857 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB
Residue 31: a UniProt-annotated variant site (in sgs)

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.Ser31= Likely benign ★ same residue
SKI p.Ser31Trp Uncertain significance ★ ⚠ same residue
SKI p.Ser31Ala Likely pathogenic ⚠ 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

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-ser31pro (accessed [today's date]).

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