Is SCARB2 p.Arg77Ser (c.231A>T) pathogenic?

SCARB2 p.Arg77Ser (c.231A>T) is classified Uncertain significance in SCARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-14). AlphaMissense: likely benign (0.1732); Very rare (popmax 8.47e-05%, nfe); Associated with progressive myoclonus epilepsy.

What condition is associated with SCARB2 p.Arg77Ser (c.231A>T)?

SCARB2 p.Arg77Ser (c.231A>T) is associated with progressive myoclonus epilepsy (ClinVar).

How common is SCARB2 p.Arg77Ser (c.231A>T) in the general population?

SCARB2 p.Arg77Ser (c.231A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SCARB2 p.Arg77Ser (c.231A>T)?

AlphaMissense predicts likely benign (score 0.1732) — an in-silico prediction, not a clinical call.

SCARB2 p.Arg77Ser

c.231A>T · rs2476284346 · VCV2178781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
AlphaMissense	0.1732	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4
Regional constraint	o/e 0.84	unconstrained · MANE · 52 kb · p 0.00017 · regional, not allelic
Overall
CADD	7.454	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,962 alleles

Overall 6.84e-05% 1/1,461,794 alleles · very rare

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.Arg77Ser
Coding: c.231A>T
MANE Select: NM_005506
dbSNP: rs2476284346
Type: single nucleotide variant
Location: chr4:76195751 (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.Arg77= Likely benign ★ 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-arg77ser (accessed [today's date]).

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