Is STAR p.Lys253= (c.759G>A) pathogenic?

STAR p.Lys253= (c.759G>A) is classified Likely benign in STAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-03). Ultra-rare (popmax 0.0495%, afr); Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Lys253= (c.759G>A)?

STAR p.Lys253= (c.759G>A) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Lys253= (c.759G>A) in the general population?

STAR p.Lys253= (c.759G>A) is ultra-rare (popmax 0.0495%, afr) (gnomAD).

STAR p.Lys253=

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.759G>A · rs146000965 · VCV1089539

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, 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.
REVEL	0.048	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.1, phastCons 1
Overall
CADD	6.941	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% African / African-American · 37/74,684 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0326%

Overall 0.00262% 42/1,600,642 alleles · ultra-rare exomes 29/1,448,312 · genomes 13/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0495%	2,018
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,206
Remaining individualsnot grpmax-eligible	0.00322%	31,028
South Asian	0.00113%	88,506
European (non-Finnish)	8.52e-05%	1,173,708

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.Lys253=
Coding: c.759G>A
MANE Select: NM_000349
dbSNP: rs146000965
Type: single nucleotide variant
Location: chr8:38144372 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 253: the start domain; an α-helix

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-lys253 (accessed [today's date]).

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