Is SKI p.Arg714= (c.2142C>T) pathogenic?

SKI p.Arg714= (c.2142C>T) is classified Likely benign in SKI (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-04). Very rare (popmax 0.000175%, nfe); Associated with Shprintzen-Goldberg syndrome.

What condition is associated with SKI p.Arg714= (c.2142C>T)?

SKI p.Arg714= (c.2142C>T) is associated with Shprintzen-Goldberg syndrome (ClinVar).

How common is SKI p.Arg714= (c.2142C>T) in the general population?

SKI p.Arg714= (c.2142C>T) is very rare (popmax 0.000175%, nfe) (gnomAD).

SKI p.Arg714=

c.2142C>T · rs1569868248 · VCV761161

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Conditions

Shprintzen-Goldberg syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.78	GERP -3.8
Overall
CADD	3.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000175% European (non-Finnish) · 2/1,142,138 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00013% 2/1,535,114 alleles · very rare exomes 2/1,382,912 · genomes 0/152,202 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SKI
Protein: p.Arg714=
Coding: c.2142C>T
MANE Select: NM_003036
dbSNP: rs1569868248
Type: single nucleotide variant
Location: chr1:2306720 (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

Disease context

Shprintzen-Goldberg syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SKI p.Arg714His Conflicting classifications of pathogenicity ★ ⚠ same residue
SKI p.Arg714Leu Uncertain significance ★ ⚠ same residue
SKI p.Arg714Cys Uncertain significance ★★ ⚠ same residue
SKI p.Arg714Gly Uncertain significance ★ ⚠ 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

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-arg714 (accessed [today's date]).

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