CASQ2 p.Arg251=
c.753C>A · rs1647551183 · VCV1759417
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00085%, nfe)
Conditions
2
Cardiovascular phenotype
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 1.9 | GERP -3.1, phastCons 1 |
| Overall | ||
| CADD | 8.348 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00085%
European (non-Finnish) · 10/1,176,958 alleles
Filtering AF
0.00043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.000685%
10/1,459,054 alleles · very rare
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
- CASQ2
- Protein
- p.Arg251=
- Coding
- c.753C>A
- MANE Select
- NM_001232
- dbSNP
- rs1647551183
- Type
- single nucleotide variant
- Location
- chr1:115725538 (GRCh38)
- Gene constraint
- LOEUF 1.322 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.63 · 4 PDB
- Residue 251
- a β-strand
Similar variants
- CASQ2 p.Arg251Cys Uncertain significance ★★ ⚠ same residue
- CASQ2 p.Arg251His Uncertain significance ★★ ⚠ same residue
- CASQ2 c.235-2A>G Likely pathogenic ★★ same condition
- CASQ2 c.319+2T>G Likely pathogenic ★★ same condition
- CASQ2 c.320-2A>G Pathogenic ★★ same condition
- CASQ2 c.420+1G>A Likely pathogenic ★★ same condition
- CASQ2 c.533-2A>G Likely pathogenic ★★ same condition
- CASQ2 c.606+1G>C 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/casq2-p-arg251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown