Is STAR p.Arg182Ser (c.544C>A) pathogenic?

STAR p.Arg182Ser (c.544C>A) is classified Likely pathogenic in STAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-26). AlphaMissense: likely pathogenic (0.9953); Very rare (popmax 8.47e-05%, nfe); Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Arg182Ser (c.544C>A)?

STAR p.Arg182Ser (c.544C>A) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Arg182Ser (c.544C>A) in the general population?

STAR p.Arg182Ser (c.544C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about STAR p.Arg182Ser (c.544C>A)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

STAR p.Arg182Ser

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.544C>A · rs369232492 · VCV3251758

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital lipoid adrenal hyperplasia due to STAR deficency

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic ✓ concordant with ClinVar · top 1% in STAR
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -15.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,542 bp · p 0.84 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.19e-05% 1/1,614,216 alleles · very rare exomes 1/1,461,872 · genomes 0/152,344 · 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: STAR
Protein: p.Arg182Ser
Coding: c.544C>A
MANE Select: NM_000349
dbSNP: rs369232492
Type: single nucleotide variant
Location: chr8:38146069 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 182: the start domain; a β-strand; a UniProt-annotated variant site (in ah1; partial loss of activity)

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.Arg182Cys Pathogenic ★★ same residue
STAR p.Arg182His Pathogenic ★★ same residue
STAR p.Arg182Leu Pathogenic ★ same residue
STAR p.Arg182Pro 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

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-arg182ser (accessed [today's date]).

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