Is RBCK1 p.Pro232= (c.696C>G) pathogenic?

RBCK1 p.Pro232= (c.696C>G) is classified Likely benign in RBCK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-11). Ultra-rare (popmax 0.0208%, eas); Associated with polyglucosan body myopathy 1 with or without immunodeficiency.

What condition is associated with RBCK1 p.Pro232= (c.696C>G)?

RBCK1 p.Pro232= (c.696C>G) is associated with polyglucosan body myopathy 1 with or without immunodeficiency (ClinVar).

How common is RBCK1 p.Pro232= (c.696C>G) in the general population?

RBCK1 p.Pro232= (c.696C>G) is ultra-rare (popmax 0.0208%, eas) (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.Pro232=

c.696C>G · rs549369680 · VCV1135593

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, eas)

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.
REVEL	0.157	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.5
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% East Asian · 9/43,218 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00805%

Overall 0.00291% 46/1,581,388 alleles · ultra-rare exomes 43/1,429,048 · genomes 3/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0208%	4,802
South Asian	0.00916%	10,922
Remaining individualsnot grpmax-eligible	0.00326%	30,692
European (non-Finnish)	0.00223%	44,862
Admixed American	0.00178%	56,160

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: RBCK1
Protein: p.Pro232=
Coding: c.696C>G
MANE Select: NM_031229
dbSNP: rs549369680
Type: single nucleotide variant
Location: chr20:419671 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34 · 11 PDB
Residue 232: the 'interaction with tab2' 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 p.Pro232_Leu247dup Uncertain significance ★ same residue
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

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-pro232 (accessed [today's date]).

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