Is SCARB2 p.Ser110Pro (c.328T>C) pathogenic?

SCARB2 p.Ser110Pro (c.328T>C) is classified Uncertain significance in SCARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: likely pathogenic (0.8842); Absent from gnomAD v4.1; Associated with progressive myoclonus epilepsy.

What condition is associated with SCARB2 p.Ser110Pro (c.328T>C)?

SCARB2 p.Ser110Pro (c.328T>C) is associated with progressive myoclonus epilepsy (ClinVar).

How common is SCARB2 p.Ser110Pro (c.328T>C) in the general population?

SCARB2 p.Ser110Pro (c.328T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCARB2 p.Ser110Pro (c.328T>C)?

AlphaMissense predicts likely pathogenic (score 0.8842) — an in-silico prediction, not a clinical call.

SCARB2 p.Ser110Pro

c.328T>C · rs2476255754 · VCV1713762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

progressive myoclonus epilepsy

Computational evidence

Protein change
AlphaMissense	0.8842	likely pathogenic
REVEL	0.634	indeterminate
SaProt	LLR -14.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 52 kb · p 0.00017 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCARB2
Protein: p.Ser110Pro
Coding: c.328T>C
MANE Select: NM_005506
dbSNP: rs2476255754
Type: single nucleotide variant
Location: chr4:76181049 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 93.01 · 10 PDB
Residue 110: a β-strand

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-ser110pro (accessed [today's date]).

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