Is STAR p.Ile166= (c.498T>C) pathogenic?

STAR p.Ile166= (c.498T>C) is classified Uncertain significance in STAR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-31). Absent from gnomAD v4.1; Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Ile166= (c.498T>C)?

STAR p.Ile166= (c.498T>C) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Ile166= (c.498T>C) in the general population?

STAR p.Ile166= (c.498T>C) is absent from gnomAD v4.1 (gnomAD).

STAR p.Ile166=

Q: How is Congenital lipoid adrenal hyperplasia due to STAR deficency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.498T>C · VCV4062006

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital lipoid adrenal hyperplasia due to STAR deficency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.076	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.84, phastCons 1
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

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: STAR
Protein: p.Ile166=
Coding: c.498T>C
MANE Select: NM_000349
Type: single nucleotide variant
Location: chr8:38146115 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 166: the start domain; a β-strand

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

Disease context

congenital lipoid adrenal hyperplasia due to STAR deficency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital lipoid adrenal hyperplasia due to STAR deficency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

STAR p.Ile166Val Uncertain significance ★ ⚠ 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
STAR p.Ala218Val 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-ile166 (accessed [today's date]).

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