Is SKI p.Pro516Gln (c.1547C>A) pathogenic?

SKI p.Pro516Gln (c.1547C>A) is classified Uncertain significance in SKI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-08). AlphaMissense: likely benign (0.158); No allele count reported in gnomAD v4.1 (AN 1,551,742).

How common is SKI p.Pro516Gln (c.1547C>A) in the general population?

SKI p.Pro516Gln (c.1547C>A) is no allele count reported in gnomAD v4.1 (AN 1,551,742) (gnomAD).

What do computational predictors say about SKI p.Pro516Gln (c.1547C>A)?

AlphaMissense predicts likely benign (score 0.158) — an in-silico prediction, not a clinical call.

SKI p.Pro516Gln

c.1547C>A · rs781193859 · VCV2579361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.158 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,742)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.158	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 77 kb · p 0.0098 · regional, not allelic
Overall
CADD	26.2	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 1,551,742). 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.Pro516Gln
Coding: c.1547C>A
MANE Select: NM_003036
dbSNP: rs781193859
Type: single nucleotide variant
Location: chr1:2304365 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.18 · 4 PDB
Residue 516: the 'disordered' region

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

Similar variants

SKI p.Pro516Leu Uncertain significance ★★ ⚠ same residue
SKI p.Pro516= 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-pro516gln (accessed [today's date]).

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