Is SCARB2 p.Pro439Arg (c.1316C>G) pathogenic?

SCARB2 p.Pro439Arg (c.1316C>G) is classified Uncertain significance in SCARB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: likely pathogenic (0.9286); Absent from gnomAD v4.1; Associated with action myoclonus-renal failure syndrome.

What condition is associated with SCARB2 p.Pro439Arg (c.1316C>G)?

SCARB2 p.Pro439Arg (c.1316C>G) is associated with action myoclonus-renal failure syndrome (ClinVar).

How common is SCARB2 p.Pro439Arg (c.1316C>G) in the general population?

SCARB2 p.Pro439Arg (c.1316C>G) is absent from gnomAD v4.1 (gnomAD).

How is Action myoclonus-renal failure syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SCARB2 p.Pro439Arg (c.1316C>G)?

AlphaMissense predicts likely pathogenic (score 0.9286) — an in-silico prediction, not a clinical call.

SCARB2 p.Pro439Arg

c.1316C>G · VCV3590845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9286 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

action myoclonus-renal failure syndrome

Computational evidence

Protein change
AlphaMissense	0.9286	likely pathogenic · top 8% in SCARB2
REVEL	0.687	pathogenic-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 52 kb · p 0.00017 · regional, not allelic
Overall
CADD	31.0	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.Pro439Arg
Coding: c.1316C>G
MANE Select: NM_005506
Type: single nucleotide variant
Location: chr4:76163307 (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

action myoclonus-renal failure syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Action myoclonus-renal failure syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult

Similar variants

SCARB2 p.Pro439Leu Uncertain significance ★ ⚠ same residue
SCARB2 p.Pro439= 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

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-pro439arg (accessed [today's date]).

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