XYLT2 p.Ser591=
c.1773C>T · rs769862588 · VCV1939299
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
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. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -3.4 |
| Overall | ||
| CADD | 11.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,072 alleles
Filtering AF
0.0213%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0205%
Overall
0.0181%
291/1,611,592 alleles · ultra-rare
exomes 276/1,459,388 · genomes 15/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,036 |
| European (non-Finnish) | 0.0237% | 4,225 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,474 |
| African / African-American | 0.00668% | 14,974 |
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
- XYLT2
- Protein
- p.Ser591=
- Coding
- c.1773C>T
- MANE Select
- NM_022167
- dbSNP
- rs769862588
- Type
- single nucleotide variant
- Location
- chr17:50357084 (GRCh38)
- Gene constraint
- LOEUF 0.689 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.79
Similar variants
- XYLT2 p.Ser591Arg Uncertain significance ★★ ⚠ same residue
- XYLT2 p.Ser591Gly Uncertain significance ★ ⚠ same residue
- XYLT2 p.Arg563Cys Likely pathogenic ★★ same type
- XYLT2 p.Ala254Val Uncertain significance ★★ ⚠ same type
- XYLT2 p.Ala543Thr Uncertain significance ★★ ⚠ same type
- XYLT2 p.Ala570Thr Uncertain significance ★★ ⚠ same type
- XYLT2 p.Ala614Val Uncertain significance ★★ ⚠ same type
- XYLT2 p.Ala807Val 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/xylt2-p-ser591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown