STAR p.Arg274Pro
c.821G>C · VCV4062015
Computational evidence
| Protein change | ||
| AlphaMissense | 0.7865 | likely pathogenic |
|---|---|---|
| REVEL | 0.617 | indeterminate |
| SaProt | LLR -14.79 | damaging |
| ⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -4.1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 6,542 bp · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 20.9 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
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
- STAR
- Protein
- p.Arg274Pro
- Coding
- c.821G>C
- MANE Select
- NM_000349
- Type
- single nucleotide variant
- Location
- chr8:38144310 (GRCh38)
- Gene constraint
- LOEUF 1.297 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.71 · 4 PDB
- Residue 274
- the start domain; an α-helix
Disease context
congenital lipoid adrenal hyperplasia due to STAR deficency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Congenital lipoid adrenal hyperplasia due to STAR deficency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy, Neonatal
Similar variants
- STAR p.Arg274Cys Uncertain significance ★ ⚠ same residue
- STAR p.Arg274His Likely benign ★ same residue
- STAR c.178+1G>C Likely pathogenic ★★ same condition
- STAR c.306+1G>A Likely pathogenic ★★ same condition
- STAR c.307-1G>C Likely pathogenic ★★ same condition
- STAR c.465+2T>C Pathogenic/Likely pathogenic ★★ same condition
- STAR c.64+1G>A Pathogenic/Likely pathogenic ★★ same condition
- STAR c.64+1G>T 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/star-p-arg274pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown