Is RYR3 p.Asp331= (c.993C>T) pathogenic?

RYR3 p.Asp331= (c.993C>T) is classified Likely benign in RYR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-13). Very rare (popmax 0.00167%, amr); Associated with Epileptic encephalopathy.

What condition is associated with RYR3 p.Asp331= (c.993C>T)?

RYR3 p.Asp331= (c.993C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is RYR3 p.Asp331= (c.993C>T) in the general population?

RYR3 p.Asp331= (c.993C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

RYR3 p.Asp331=

c.993C>T · rs1456880473 · VCV1092606

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Epileptic encephalopathy

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 0.87	GERP 0.25, phastCons 1
Overall
CADD	7.433	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,924 alleles

Overall 0.000186% 3/1,612,302 alleles · very rare exomes 2/1,460,180 · genomes 1/152,122 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,924
Remaining individualsnot grpmax-eligible	0.0016%	62,400
European (non-Finnish)	8.48e-05%	1,178,794

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: RYR3
Protein: p.Asp331=
Coding: c.993C>T
MANE Select: NM_001036
dbSNP: rs1456880473
Type: single nucleotide variant
Location: chr15:33562857 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Residue 331: the mir 4 domain

Full RYR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

RYR3 p.Asp331Asn Uncertain significance ★ same residue
RYR3 c.10758+6C>G Uncertain significance ★★ same condition
RYR3 c.10995+5C>T Uncertain significance ★★ same condition
RYR3 c.12978+3A>G Uncertain significance ★★ same condition
RYR3 p.Ala1179Thr Uncertain significance ★★ ⚠ same condition
RYR3 p.Ala1331Thr Uncertain significance ★★ ⚠ same condition
RYR3 p.Ala1570Thr Uncertain significance ★★ ⚠ same condition
RYR3 p.Ala1579Thr 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/ryr3-p-asp331 (accessed [today's date]).

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