FKRP p.Arg265=
c.795G>C · rs1364305668 · VCV1124531
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0305%, amr)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.35 | GERP -1.2, phastCons 0.99 |
| Overall | ||
| CADD | 1.478 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0305%
Admixed American · 12/39,402 alleles
Filtering AF
0.0176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.000963%
14/1,453,188 alleles · ultra-rare
exomes 10/1,302,520 · genomes 4/150,668 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0305% | 3,284 |
| Remaining individualsnot grpmax-eligible | 0.00179% | 55,932 |
| African / African-American | 0.00147% | 68,220 |
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
- FKRP
- Protein
- p.Arg265=
- Coding
- c.795G>C
- MANE Select
- NM_024301
- dbSNP
- rs1364305668
- Type
- single nucleotide variant
- Location
- chr19:46756245 (GRCh38)
- Gene constraint
- LOEUF 1.543 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.08 · 8 PDB
- Residue 265
- an α-helix
Similar variants
- FKRP p.Arg265Leu Uncertain significance ★★ ⚠ same residue
- FKRP p.Arg265Gln Uncertain significance ★ ⚠ same residue
- FKRP p.Arg265Pro Uncertain significance ⚠ same residue
- FKRP p.Ala157Pro Pathogenic/Likely pathogenic ★★ same condition
- FKRP p.Ala321Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- FKRP p.Ala455Asp Pathogenic ★★ same condition
- FKRP p.Arg176Ter Pathogenic/Likely pathogenic ★★ same condition
- FKRP p.Arg275Cys 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/fkrp-p-arg265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown