Is RYR3 p.Arg2001= (c.6003G>A) pathogenic?

RYR3 p.Arg2001= (c.6003G>A) is classified Likely benign in RYR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-20). Very rare (popmax 0.00268%, afr); Associated with Epileptic encephalopathy.

What condition is associated with RYR3 p.Arg2001= (c.6003G>A)?

RYR3 p.Arg2001= (c.6003G>A) is associated with Epileptic encephalopathy (ClinVar).

How common is RYR3 p.Arg2001= (c.6003G>A) in the general population?

RYR3 p.Arg2001= (c.6003G>A) is very rare (popmax 0.00268%, afr) (gnomAD).

RYR3 p.Arg2001=

c.6003G>A · rs946067814 · VCV1078472

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.2	GERP -3.5, phastCons 0.045
Overall
CADD	4.917	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,730 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,364 alleles · very rare exomes 0/1,461,696 · genomes 2/151,668 · joint denominator

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.Arg2001=
Coding: c.6003G>A
MANE Select: NM_001036
dbSNP: rs946067814
Type: single nucleotide variant
Location: chr15:33696360 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Residue 2001: the '4 x approximate repeats' region

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.Arg2001Gln 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-arg2001 (accessed [today's date]).

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