PTPRF p.Ala221=
c.663G>A · rs540168118 · VCV793336
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.75%, sas)
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 | GERP -4.5 |
| Overall | ||
| CADD | 12.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.75%
South Asian · 683/91,086 alleles
Filtering AF
0.703%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.685%
Overall
0.0462%
746/1,614,186 alleles · rare
exomes 713/1,461,836 · genomes 33/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.75% | 133 |
| Middle Eastern | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,084 |
| Admixed American | 0.0167% | 6,003 |
| European (non-Finnish) | 0.00169% | 59,001 |
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
- PTPRF
- Protein
- p.Ala221=
- Coding
- c.663G>A
- MANE Select
- NM_002840
- dbSNP
- rs540168118
- Type
- single nucleotide variant
- Location
- chr1:43578904 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.43 · 13 PDB
- Residue 221
- the ig-like c2-type 2 domain; a β-strand
Similar variants
- PTPRF p.Gly1143Ser Uncertain significance ★★ ⚠ same type
- PTPRF p.His1730Gln Uncertain significance ★★ ⚠ same type
- PTPRF c.1531+9G>A Benign/Likely benign ★★ same type
- PTPRF c.1668+10G>C Benign/Likely benign ★★ same type
- PTPRF c.237+5G>A Benign ★★ same type
- PTPRF c.3974-9C>T Benign ★★ same type
- PTPRF p.Ala1659= Benign ★★ same type
- PTPRF p.Ala356Ser Likely benign ★★ 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/ptprf-p-ala221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown