Is RYR1 p.Pro4472= (c.13416C>T) pathogenic?

RYR1 p.Pro4472= (c.13416C>T) is classified Uncertain significance in RYR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). No allele count reported in gnomAD v4.1 (AN 1,416,824); Associated with malignant hyperthermia, susceptibility to, 1.

What condition is associated with RYR1 p.Pro4472= (c.13416C>T)?

RYR1 p.Pro4472= (c.13416C>T) is associated with malignant hyperthermia, susceptibility to, 1 (ClinVar).

How common is RYR1 p.Pro4472= (c.13416C>T) in the general population?

RYR1 p.Pro4472= (c.13416C>T) is no allele count reported in gnomAD v4.1 (AN 1,416,824) (gnomAD).

RYR1 p.Pro4472=

c.13416C>T · rs2514682538 · VCV3069481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,416,824)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -2.3
Overall
CADD	3.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,416,824). 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: RYR1
Protein: p.Pro4472=
Coding: c.13416C>T
MANE Select: NM_000540
dbSNP: rs2514682538
Type: single nucleotide variant
Location: chr19:38565750 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4472: 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.Pro4472Arg Uncertain significance ★★ same residue
RYR1 p.Pro4472Ser 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-pro4472 (accessed [today's date]).

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