PTDSS1 p.Phe58=
c.174T>C · VCV3604996
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.07%, 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 0.43 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 14.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.07%
Middle Eastern · 4/5,716 alleles
Filtering AF
0.0239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0143%
Overall
0.000714%
11/1,540,860 alleles · ultra-rare
exomes 10/1,390,324 · genomes 1/150,536 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.07% | 1,429 |
| Remaining individualsnot grpmax-eligible | 0.00173% | 57,690 |
| European (non-Finnish) | 0.000529% | 189,207 |
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
- PTDSS1
- Protein
- p.Phe58=
- Coding
- c.174T>C
- MANE Select
- NM_014754
- Type
- single nucleotide variant
- Location
- chr8:96262214 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.33 · 6 PDB
- Residue 58
- an α-helix
Similar variants
- PTDSS1 p.Arg95Gln Pathogenic/Likely pathogenic ★★ same type
- PTDSS1 p.Ala140Thr Uncertain significance ★★ ⚠ same type
- PTDSS1 p.Arg238Gln Uncertain significance ★★ ⚠ same type
- PTDSS1 p.Glu212Lys Uncertain significance ★★ ⚠ same type
- PTDSS1 p.Gly229Asp Uncertain significance ★★ ⚠ same type
- PTDSS1 p.His246Gln Uncertain significance ★★ ⚠ same type
- PTDSS1 p.Leu292Phe Uncertain significance ★★ ⚠ same type
- PTDSS1 p.Leu307Trp 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/ptdss1-p-phe58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown