PTPRF p.Ala648=
c.1944G>A · rs376955084 · VCV2638759
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0458%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.072 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -4.1 |
| Overall | ||
| CADD | 6.153 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0458%
European (non-Finnish) · 540/1,177,802 alleles
Filtering AF
0.0426%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0414%
Overall
0.037%
595/1,608,092 alleles · ultra-rare
exomes 558/1,455,846 · genomes 37/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0458% | 2,181 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0408% | 2,451 |
| Remaining individualsnot grpmax-eligible | 0.0289% | 3,457 |
| Middle Eastern | 0.0165% | 6,070 |
| Admixed American | 0.0135% | 7,416 |
| Finnishnot grpmax-eligible | 0.0126% | 7,918 |
| South Asian | 0.00447% | 22,362 |
| African / African-American | 0.00401% | 24,966 |
| East Asian | 0.00224% | 44,662 |
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.Ala648=
- Coding
- c.1944G>A
- MANE Select
- NM_002840
- dbSNP
- rs376955084
- Type
- single nucleotide variant
- Location
- chr1:43597878 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.43 · 13 PDB
- Residue 648
- a β-strand; the fibronectin type-iii 4 domain
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-ala648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown