Is RYR1 p.Ser1007= (c.3021C>T) pathogenic?

RYR1 p.Ser1007= (c.3021C>T) is classified Likely benign in RYR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). Very rare (popmax 0.00695%, nfe); Associated with RYR1-related disorder.

What condition is associated with RYR1 p.Ser1007= (c.3021C>T)?

RYR1 p.Ser1007= (c.3021C>T) is associated with RYR1-related disorder, malignant hyperthermia, susceptibility to, 1 (ClinVar).

How common is RYR1 p.Ser1007= (c.3021C>T) in the general population?

RYR1 p.Ser1007= (c.3021C>T) is very rare (popmax 0.00695%, nfe) (gnomAD).

RYR1 p.Ser1007=

c.3021C>T · rs143891703 · VCV329005

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Conditions

RYR1-related disorder

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 -10	GERP -3.7
Overall
CADD	1.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% European (non-Finnish) · 82/1,179,956 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00558% 90/1,613,238 alleles · very rare exomes 86/1,461,044 · genomes 4/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,390
Finnishnot grpmax-eligible	0.00473%	21,128
African / African-American	0.00267%	37,464
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,464
South Asian	0.0011%	91,072

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: RYR1
Protein: p.Ser1007=
Coding: c.3021C>T
MANE Select: NM_000540
dbSNP: rs143891703
Type: single nucleotide variant
Location: chr19:38466241 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1007: the '6 x approximate repeats' region

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

Disease context

Also linked: malignant hyperthermia, susceptibility to, 1

Similar variants

RYR1 p.Ser1007Arg 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
RYR1 p.Ala2200Val 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-ser1007 (accessed [today's date]).

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