Is RBCK1 p.Pro291= (c.873C>A) pathogenic?

RBCK1 p.Pro291= (c.873C>A) is classified Likely benign in RBCK1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-04). No allele count reported in gnomAD v4.1 (AN 1,564,554); Associated with polyglucosan body myopathy 1 with or without immunodeficiency.

What condition is associated with RBCK1 p.Pro291= (c.873C>A)?

RBCK1 p.Pro291= (c.873C>A) is associated with polyglucosan body myopathy 1 with or without immunodeficiency (ClinVar).

How common is RBCK1 p.Pro291= (c.873C>A) in the general population?

RBCK1 p.Pro291= (c.873C>A) is no allele count reported in gnomAD v4.1 (AN 1,564,554) (gnomAD).

How is Polyglucosan body myopathy type 1 inherited?

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

RBCK1 p.Pro291=

c.873C>A · rs1470415932 · VCV2693321

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,564,554)

Conditions

polyglucosan body myopathy 1 with or without immunodeficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.6	GERP -4.8
Overall
CADD	7.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,564,554). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RBCK1
Protein: p.Pro291=
Coding: c.873C>A
MANE Select: NM_031229
dbSNP: rs1470415932
Type: single nucleotide variant
Location: chr20:420987 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34 · 11 PDB
Residue 291: the 'triad supradomain' region

Full RBCK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polyglucosan body myopathy 1 with or without immunodeficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Polyglucosan body myopathy type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

RBCK1 c.1308+1G>T Pathogenic/Likely pathogenic ★★ same condition
RBCK1 c.582+1G>A Likely pathogenic ★★ same condition
RBCK1 p.Arg352Ter Pathogenic ★★ same condition
RBCK1 p.Gln249Ter Pathogenic/Likely pathogenic ★★ same condition
RBCK1 c.-9C>A Uncertain significance ★★ same condition
RBCK1 p.Ala20Val Uncertain significance ★★ ⚠ same condition
RBCK1 p.Ala228Thr Uncertain significance ★★ ⚠ same condition
RBCK1 p.Ala280Val 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/rbck1-p-pro291 (accessed [today's date]).

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