Is SCARB2 p.Arg3= (c.9A>G) pathogenic?

SCARB2 p.Arg3= (c.9A>G) is classified Likely benign in SCARB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-03). Very rare (popmax 0.00526%, nfe); Associated with progressive myoclonus epilepsy.

What condition is associated with SCARB2 p.Arg3= (c.9A>G)?

SCARB2 p.Arg3= (c.9A>G) is associated with progressive myoclonus epilepsy (ClinVar).

How common is SCARB2 p.Arg3= (c.9A>G) in the general population?

SCARB2 p.Arg3= (c.9A>G) is very rare (popmax 0.00526%, nfe) (gnomAD).

SCARB2 p.Arg3=

c.9A>G · rs148558907 · VCV507452

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00526%, nfe)

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.075	GERP -4.5, phastCons 0.78
Overall
CADD	10.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00526% European (non-Finnish) · 62/1,177,906 alleles

Filtering AF 0.00419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00404% 65/1,608,804 alleles · very rare exomes 60/1,456,604 · genomes 5/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00526%	18,998
African / African-American	0.00267%	37,439
Admixed American	0.00168%	59,380

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: SCARB2
Protein: p.Arg3=
Coding: c.9A>G
MANE Select: NM_005506
dbSNP: rs148558907
Type: single nucleotide variant
Location: chr4:76213535 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 93.01 · 10 PDB

Full SCARB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonus epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCARB2 p.Arg3Gln Uncertain significance ★ ⚠ same residue
SCARB2 c.704+1G>A Pathogenic ★★ same condition
SCARB2 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same condition
SCARB2 p.Arg424Ter Pathogenic ★★ same condition
SCARB2 p.Gln288Ter Pathogenic ★★ same condition
SCARB2 p.Gln30Ter Pathogenic/Likely pathogenic ★★ same condition
SCARB2 c.1188-3T>C Uncertain significance ★★ same condition
SCARB2 c.612+5G>A Uncertain significance ★★ 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/scarb2-p-arg3 (accessed [today's date]).

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