Is SKI p.Leu32Val (c.94C>G) pathogenic?

SKI p.Leu32Val (c.94C>G) is classified Pathogenic in SKI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2018-12-20). AlphaMissense: likely pathogenic (0.8784); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SKI p.Leu32Val (c.94C>G)?

SKI p.Leu32Val (c.94C>G) is associated with Inborn genetic diseases, Shprintzen-Goldberg syndrome (ClinVar).

How common is SKI p.Leu32Val (c.94C>G) in the general population?

SKI p.Leu32Val (c.94C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SKI p.Leu32Val (c.94C>G)?

AlphaMissense predicts likely pathogenic (score 0.8784) — an in-silico prediction, not a clinical call.

SKI p.Leu32Val

c.94C>G · rs387907304 · VCV37259

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8784 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8784	likely pathogenic ✓ concordant with ClinVar
REVEL	0.617	indeterminate
SaProt	LLR -7.49	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 1	GERP -1.4, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 253 bp · p 0.099 · regional, not allelic
Overall
CADD	20.6	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

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.Leu32Val
Coding: c.94C>G
MANE Select: NM_003036
dbSNP: rs387907304
Type: single nucleotide variant
Location: chr1:2228860 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB
Residue 32: a UniProt-annotated variant site (in sgs)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Shprintzen-Goldberg syndrome

Similar variants

SKI p.Leu32= Likely benign ★★ 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.Pro35Ser 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-leu32val (accessed [today's date]).

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