Is STAR p.Pro229= (c.687G>A) pathogenic?

STAR p.Pro229= (c.687G>A) is classified Conflicting classifications of pathogenicity in STAR (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.606%, afr); Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Pro229= (c.687G>A)?

STAR p.Pro229= (c.687G>A) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Pro229= (c.687G>A) in the general population?

STAR p.Pro229= (c.687G>A) is rare (popmax 0.606%, afr) (gnomAD).

STAR p.Pro229=

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.687G>A · rs35852516 · VCV778392

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.606%, afr)

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.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.5	GERP -4.6
Overall
CADD	1.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.606% African / African-American · 455/75,044 alleles

Filtering AF 0.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.542%

Overall 0.0449% 724/1,614,154 alleles · rare exomes 461/1,461,866 · genomes 263/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.606%	165
Middle Eastern	0.429%	233
South Asian	0.124%	806
Remaining individualsnot grpmax-eligible	0.0944%	1,059
Admixed American	0.0566%	1,765
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00305%	32,778

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.Pro229=
Coding: c.687G>A
MANE Select: NM_000349
dbSNP: rs35852516
Type: single nucleotide variant
Location: chr8:38145279 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 229: 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 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
STAR p.Arg182Cys 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-pro229 (accessed [today's date]).

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