Is STAR p.Pro210fs (c.629_630del) pathogenic?

STAR p.Pro210fs (c.629630del) is classified Pathogenic in STAR (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-17). Very rare (popmax 8.47e-05%, nfe); Associated with congenital lipoid adrenal hyperplasia due to STAR deficency.

What condition is associated with STAR p.Pro210fs (c.629_630del)?

STAR p.Pro210fs (c.629_630del) is associated with congenital lipoid adrenal hyperplasia due to STAR deficency (ClinVar).

How common is STAR p.Pro210fs (c.629_630del) in the general population?

STAR p.Pro210fs (c.629_630del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

STAR p.Pro210fs

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.629_630del · rs771895449 · VCV370502

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 1.4, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,052 alleles

Overall 6.2e-05% 1/1,614,024 alleles · very rare exomes 0/1,461,782 · genomes 1/152,242 · 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.Pro210fs
Coding: c.629_630del
MANE Select: NM_000349
dbSNP: rs771895449
Type: Deletion
Location: chr8:38145983 (GRCh38)
Gene constraint: LOEUF 1.297 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.71 · 4 PDB
Residue 210: the start domain

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.Glu136fs Pathogenic ★★ same condition
STAR p.Gly232fs Pathogenic ★★ same condition
STAR p.Leu271fs Pathogenic/Likely pathogenic ★★ same condition
STAR p.Lys238fs Pathogenic ★★ same condition
STAR p.Ser46fs Pathogenic/Likely pathogenic ★★ same condition
STAR p.Thr240fs Pathogenic ★★ same condition
STAR p.Val226fs Pathogenic/Likely pathogenic ★★ same condition
STAR c.745-1_757del 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-pro210fs (accessed [today's date]).

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