KLF1 p.Pro227=
c.681C>A · rs899654024 · VCV2898432
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00943%, amr)
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 -2.8 |
| Overall | ||
| CADD | 0.479 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00943%
Admixed American · 5/53,004 alleles
Filtering AF
0.0037%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0024%
Overall
0.000509%
8/1,571,856 alleles · very rare
exomes 8/1,419,516 · genomes 0/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00943% | 10,601 |
| European (non-Finnish) | 0.000259% | 386,497 |
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
- KLF1
- Protein
- p.Pro227=
- Coding
- c.681C>A
- MANE Select
- NM_006563
- dbSNP
- rs899654024
- Type
- single nucleotide variant
- Location
- chr19:12885549 (GRCh38)
- Gene constraint
- LOEUF 1.777 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.11 · 3 PDB
- Residue 227
- a UniProt-annotated variant site (in cdan4b; likely pathogenic); a UniProt-annotated variant site (in blood group-in(lu))
Similar variants
- KLF1 p.Pro227Leu Uncertain significance ★ ⚠ same residue
- KLF1 p.Ala298Pro Pathogenic ★★ same type
- KLF1 c.*263C>T Uncertain significance ★★ same type
- KLF1 p.Ala142Val Uncertain significance ★★ ⚠ same type
- KLF1 p.Ala165Ser Uncertain significance ★★ ⚠ same type
- KLF1 p.Ala262Ser Uncertain significance ★★ ⚠ same type
- KLF1 p.Arg137Cys Uncertain significance ★★ ⚠ same type
- KLF1 p.Arg328His Uncertain significance ★★ ⚠ same type
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/klf1-p-pro227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown