Is RYR2 p.Ile4635del (c.13904_13906del) pathogenic?

RYR2 p.Ile4635del (c.1390413906del) is classified Uncertain significance in RYR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-05). No gnomAD frequency available for this variant; Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with RYR2 p.Ile4635del (c.13904_13906del)?

RYR2 p.Ile4635del (c.13904_13906del) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is RYR2 p.Ile4635del (c.13904_13906del) in the general population?

RYR2 p.Ile4635del (c.13904_13906del) is no gnomAD frequency available for this variant (gnomAD).

RYR2 p.Ile4635del

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.13904_13906del · rs2527950731 · VCV2134453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

catecholaminergic polymorphic ventricular tachycardia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.1	GERP -3.1, phastCons 0.18

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: RYR2
Protein: p.Ile4635del
Coding: c.13904_13906del
MANE Select: NM_001035
dbSNP: rs2527950731
Type: Deletion
Location: chr1:237793987 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 4635: an α-helix

Full RYR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

catecholaminergic polymorphic ventricular tachycardia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

RYR2 p.Ile4635Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
RYR2 c.10231-13del Uncertain significance ★★ same condition
RYR2 c.11039+4del Uncertain significance ★★ same condition
RYR2 c.11880+3_11880+6del Uncertain significance ★★ same condition
RYR2 c.2396+3_2396+12del Uncertain significance ★★ same condition
RYR2 c.9128+5del Uncertain significance ★★ same condition
RYR2 p.Arg3345fs Uncertain significance ★★ same condition
RYR2 p.Asp602fs 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/ryr2-p-ile4635del (accessed [today's date]).

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