Is RBCK1 p.Arg306= (c.916A>C) pathogenic?

RBCK1 p.Arg306= (c.916A>C) is classified Uncertain significance in RBCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). Very rare (popmax 0.00563%, amr); Associated with polyglucosan body myopathy 1 with or without immunodeficiency.

What condition is associated with RBCK1 p.Arg306= (c.916A>C)?

RBCK1 p.Arg306= (c.916A>C) is associated with polyglucosan body myopathy 1 with or without immunodeficiency (ClinVar).

How common is RBCK1 p.Arg306= (c.916A>C) in the general population?

RBCK1 p.Arg306= (c.916A>C) is very rare (popmax 0.00563%, amr) (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.Arg306=

c.916A>C · rs1438078445 · VCV662338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00563%, amr)

Conditions

polyglucosan body myopathy 1 with or without immunodeficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.72	donor loss · deltas
Pangolin	Δ0.51	loss · gain 0.16 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00563% Admixed American · 3/53,312 alleles

Filtering AF 0.00149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000814%

Overall 0.000323% 5/1,549,550 alleles · very rare exomes 5/1,397,670 · genomes 0/151,880 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00563%	17,771
European (non-Finnish)	0.000175%	573,017

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.Arg306=
Coding: c.916A>C
MANE Select: NM_031229
dbSNP: rs1438078445
Type: single nucleotide variant
Location: chr20:421030 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34 · 11 PDB
Residue 306: the 'triad supradomain' region; an α-helix

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-arg306 (accessed [today's date]).

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