FKRP p.Pro448=
c.1344G>T · rs754446767 · VCV1533606
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00224%, 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 -6.4 | GERP -2.9 |
| Overall | ||
| CADD | 0.391 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
South Asian · 2/89,412 alleles
Filtering AF
0.000371%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000139%
Overall
0.000138%
2/1,448,636 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
- FKRP
- Protein
- p.Pro448=
- Coding
- c.1344G>T
- MANE Select
- NM_024301
- dbSNP
- rs754446767
- Type
- single nucleotide variant
- Location
- chr19:46756794 (GRCh38)
- Gene constraint
- LOEUF 1.543 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.08 · 8 PDB
- Residue 448
- a UniProt-annotated variant site (in mddgb5; strongly reduced secretion to the medium; localizes mainly to the er compartment); a β-strand
Similar variants
- FKRP p.Pro448Leu Pathogenic/Likely 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-pro448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown