PTPRF p.Ala549=
c.1647G>A · rs370698404 · VCV721559
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.037 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.9 |
| Overall | ||
| CADD | 2.537 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,082 alleles
Filtering AF
0.00702%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00652%
Overall
0.007%
113/1,613,558 alleles · ultra-rare
exomes 100/1,461,386 · genomes 13/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,041 |
| East Asian | 0.00891% | 11,222 |
| European (non-Finnish) | 0.00839% | 11,919 |
| Finnishnot grpmax-eligible | 0.00472% | 21,200 |
| South Asian | 0.00329% | 30,361 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
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.Ala549=
- Coding
- c.1647G>A
- MANE Select
- NM_002840
- dbSNP
- rs370698404
- Type
- single nucleotide variant
- Location
- chr1:43591927 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.43 · 13 PDB
- Residue 549
- the fibronectin type-iii 3 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-ala549 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown