XPR1 p.Ile577=
c.1731C>T · rs775680476 · VCV742585
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00542%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 12.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00542%
European (non-Finnish) · 64/1,180,014 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00396%
Overall
0.00409%
66/1,614,050 alleles · very rare
exomes 63/1,461,824 · genomes 3/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00542% | 18,438 |
| Admixed American | 0.00167% | 60,012 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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
- XPR1
- Protein
- p.Ile577=
- Coding
- c.1731C>T
- MANE Select
- NM_004736
- dbSNP
- rs775680476
- Type
- single nucleotide variant
- Location
- chr1:180873865 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.31 · 51 PDB
- Residue 577
- an α-helix; the exs domain
Similar variants
- XPR1 p.Ile577Val Uncertain significance ★ ⚠ same residue
- XPR1 p.Ala254= Uncertain significance ★★ same type
- XPR1 p.Ala572Val Uncertain significance ★★ ⚠ same type
- XPR1 p.Arg110Cys Uncertain significance ★★ ⚠ same type
- XPR1 p.Arg176Ter Uncertain significance ★★ same type
- XPR1 p.Arg604Gln Uncertain significance ★★ ⚠ same type
- XPR1 p.Arg653Gln Uncertain significance ★★ ⚠ same type
- XPR1 p.Arg655Gly 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/xpr1-p-ile577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown