FKRP p.Val218=
c.654G>A · rs749320485 · VCV702486
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0422%, sas)
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 7 | GERP 0.99, phastCons 1 |
| Overall | ||
| CADD | 5.729 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0422%
South Asian · 35/82,864 alleles
Filtering AF
0.0312%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0273%
Overall
0.00319%
44/1,380,542 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0422% | 2,368 |
| Remaining individualsnot grpmax-eligible | 0.00169% | 59,180 |
| European (non-Finnish) | 0.000696% | 143,672 |
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.Val218=
- Coding
- c.654G>A
- MANE Select
- NM_024301
- dbSNP
- rs749320485
- Type
- single nucleotide variant
- Location
- chr19:46756104 (GRCh38)
- Gene constraint
- LOEUF 1.543 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.08 · 8 PDB
- Residue 218
- an α-helix
Similar variants
- FKRP p.Val218fs Pathogenic ★ 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
- FKRP p.Arg54Gly Likely pathogenic ★★ ⚠ same condition
- FKRP p.Asn463Asp 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-val218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown