Is STAR p.Ser254= (c.762C>T) pathogenic?

STAR p.Ser254= (c.762C>T) is classified Uncertain significance in STAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-02). Very rare (popmax 8.51e-05%, nfe); Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Ser254= (c.762C>T)?

STAR p.Ser254= (c.762C>T) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Ser254= (c.762C>T) in the general population?

STAR p.Ser254= (c.762C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

STAR p.Ser254=

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.762C>T · VCV3595554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

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	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.2
Overall
CADD	0.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,174,608 alleles

Overall 6.24e-05% 1/1,602,484 alleles · very rare exomes 1/1,450,138 · genomes 0/152,346 · 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.Ser254=
Coding: c.762C>T
MANE Select: NM_000349
Type: single nucleotide variant
Location: chr8:38144369 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 254: 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-ser254 (accessed [today's date]).

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