Is RYR2 p.Asp3Val (c.8A>T) pathogenic?

RYR2 p.Asp3Val (c.8A>T) is classified Uncertain significance in RYR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). AlphaMissense: ambiguous (0.3642); No allele count reported in gnomAD v4.1 (AN 1,257,098); Associated with catecholaminergic polymorphic ventricular tachycardia.

What condition is associated with RYR2 p.Asp3Val (c.8A>T)?

RYR2 p.Asp3Val (c.8A>T) is associated with catecholaminergic polymorphic ventricular tachycardia (ClinVar).

How common is RYR2 p.Asp3Val (c.8A>T) in the general population?

RYR2 p.Asp3Val (c.8A>T) is no allele count reported in gnomAD v4.1 (AN 1,257,098) (gnomAD).

What do computational predictors say about RYR2 p.Asp3Val (c.8A>T)?

AlphaMissense predicts ambiguous (score 0.3642) — an in-silico prediction, not a clinical call.

RYR2 p.Asp3Val

Q: How is Catecholaminergic polymorphic ventricular tachycardia inherited?

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

c.8A>T · rs2527003162 · VCV3071128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3642 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,257,098)

Conditions

catecholaminergic polymorphic ventricular tachycardia

Computational evidence

Protein change
AlphaMissense	0.3642	ambiguous
REVEL	0.417	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 335 kb · p 0.00039 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,257,098). 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.Asp3Val
Coding: c.8A>T
MANE Select: NM_001035
dbSNP: rs2527003162
Type: single nucleotide variant
Location: chr1:237042529 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

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

Disease context

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

For Catecholaminergic polymorphic ventricular tachycardia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RYR2 p.Asp3Glu Uncertain significance ★ ⚠ same residue
RYR2 p.Asp3Tyr Uncertain significance ★★ same residue
RYR2 p.Ala2387Thr Pathogenic/Likely pathogenic ★★ same condition
RYR2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same condition
RYR2 p.Arg420Trp Pathogenic ★★ same condition
RYR2 p.Ile4867Thr Pathogenic/Likely pathogenic ★★ same condition
RYR2 p.Leu433Pro Pathogenic ★★ same condition
RYR2 p.Tyr4725Cys Pathogenic/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/ryr2-p-asp3val (accessed [today's date]).

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