Is RYR2 p.Phe782= (c.2346C>T) pathogenic?

RYR2 p.Phe782= (c.2346C>T) is classified Likely benign in RYR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-06). Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with RYR2 p.Phe782= (c.2346C>T)?

RYR2 p.Phe782= (c.2346C>T) is associated with cardiomyopathy (ClinVar).

How common is RYR2 p.Phe782= (c.2346C>T) in the general population?

RYR2 p.Phe782= (c.2346C>T) is absent from gnomAD v4.1 (gnomAD).

RYR2 p.Phe782=

c.2346C>T · rs2150477024 · VCV1332365

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cardiomyopathy

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 5.9	GERP 2.8, phastCons 1
Overall
CADD	13.25	PHRED · no single calibrated threshold — expert panels disagree

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: RYR2
Protein: p.Phe782=
Coding: c.2346C>T
MANE Select: NM_001035
dbSNP: rs2150477024
Type: single nucleotide variant
Location: chr1:237500853 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 782: the b30.2/spry 1 domain

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

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RYR2 p.Arg420Trp Pathogenic ★★ same condition
RYR2 p.Arg4497Cys Pathogenic ★★ same condition
RYR2 p.Asn4763Ser Pathogenic/Likely pathogenic ★★ same condition
RYR2 p.Gly357Ser Pathogenic ★★ same condition
RYR2 p.Met3978Ile Pathogenic/Likely pathogenic ★★ same condition
RYR2 p.Ser2246Leu Pathogenic ★★ same condition
RYR2 c.10554+6C>A Uncertain significance ★★ same condition
RYR2 c.10936-2A>G 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-phe782 (accessed [today's date]).

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