Is SCARB2 p.Pro193= (c.579C>T) pathogenic?

SCARB2 p.Pro193= (c.579C>T) is classified Likely benign in SCARB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-16). Very rare (popmax 0.00933%, afr); Associated with progressive myoclonus epilepsy.

What condition is associated with SCARB2 p.Pro193= (c.579C>T)?

SCARB2 p.Pro193= (c.579C>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is SCARB2 p.Pro193= (c.579C>T) in the general population?

SCARB2 p.Pro193= (c.579C>T) is very rare (popmax 0.00933%, afr) (gnomAD).

SCARB2 p.Pro193=

c.579C>T · rs148029250 · VCV589990

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00933%, 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 -9.5	GERP -4.5
Overall
CADD	0.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00933% African / African-American · 7/75,040 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.00322% 52/1,614,096 alleles · very rare exomes 49/1,461,810 · genomes 3/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,720
South Asian	0.00769%	13,011
Admixed American	0.00333%	30,011
European (non-Finnish)	0.00297%	33,714
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Pro193=
Coding: c.579C>T
MANE Select: NM_005506
dbSNP: rs148029250
Type: single nucleotide variant
Location: chr4:76179550 (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-pro193 (accessed [today's date]).

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