Is SCARB2 p.Phe6= (c.18C>T) pathogenic?

SCARB2 p.Phe6= (c.18C>T) is classified Likely benign in SCARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). Very rare (popmax 0.00133%, afr); Associated with progressive myoclonus epilepsy.

What condition is associated with SCARB2 p.Phe6= (c.18C>T)?

SCARB2 p.Phe6= (c.18C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is SCARB2 p.Phe6= (c.18C>T) in the general population?

SCARB2 p.Phe6= (c.18C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

SCARB2 p.Phe6=

c.18C>T · rs1733112720 · VCV1625894

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 4.7	GERP 1.5, phastCons 1
Overall
CADD	13.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,610,364 alleles · very rare exomes 3/1,458,112 · genomes 1/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,914
European (non-Finnish)	0.000255%	392,861

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.Phe6=
Coding: c.18C>T
MANE Select: NM_005506
dbSNP: rs1733112720
Type: single nucleotide variant
Location: chr4:76213526 (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 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
SCARB2 c.704+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-phe6 (accessed [today's date]).

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