Is RYR1 p.Pro4530= (c.13590C>T) pathogenic?

RYR1 p.Pro4530= (c.13590C>T) is classified Likely benign in RYR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). Absent from gnomAD v4.1; Associated with malignant hyperthermia, susceptibility to, 1.

What condition is associated with RYR1 p.Pro4530= (c.13590C>T)?

RYR1 p.Pro4530= (c.13590C>T) is associated with malignant hyperthermia, susceptibility to, 1 (ClinVar).

How common is RYR1 p.Pro4530= (c.13590C>T) in the general population?

RYR1 p.Pro4530= (c.13590C>T) is absent from gnomAD v4.1 (gnomAD).

RYR1 p.Pro4530=

c.13590C>T · VCV3385601

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

malignant hyperthermia, susceptibility to, 1

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 -2.4	GERP -3.6
Overall
CADD	1.835	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: RYR1
Protein: p.Pro4530=
Coding: c.13590C>T
MANE Select: NM_000540
Type: single nucleotide variant
Location: chr19:38567848 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4530: the 'disordered' region

Full RYR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

malignant hyperthermia, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RYR1 p.Pro4530Leu Uncertain significance ★★ ⚠ same residue
RYR1 p.Pro4530Ser Uncertain significance ★ same residue
RYR1 c.10347+1G>A Pathogenic ★★★ same condition
RYR1 c.10348-6C>G Pathogenic ★★★ same condition
RYR1 c.1925+1G>C Likely pathogenic ★★★ same condition
RYR1 c.8310+1G>T Pathogenic ★★★ same condition
RYR1 c.9472+1G>A Pathogenic ★★★ same condition
RYR1 p.Ala152Asp Likely pathogenic ★★★ 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/ryr1-p-pro4530 (accessed [today's date]).

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