CTPS2 p.Phe59=
c.177C>T · rs748620326 · VCV2660067
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0092%, afr)
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 3.7 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 8.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0092%
African / African-American · 5/54,355 alleles
Filtering AF
0.00353%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00235%
Overall
0.00113%
13/1,148,531 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0092% | 10,871 |
| Remaining individualsnot grpmax-eligible | 0.00442% | 22,604 |
| East Asian | 0.00322% | 31,081 |
| European (non-Finnish) | 0.000575% | 173,822 |
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
- CTPS2
- Protein
- p.Phe59=
- Coding
- c.177C>T
- MANE Select
- NM_175859
- dbSNP
- rs748620326
- Type
- single nucleotide variant
- Location
- chrX:16699083 (GRCh38)
- Structure
- AlphaFold pLDDT 91.79 · 8 PDB
- Residue 59
- a β-strand
Similar variants
- CTPS2 p.Gly542= Benign ★★ same type
- CTPS2 p.Ala315Thr Conflicting classifications of pathogenicity ★ ⚠ same type
- CTPS2 p.Ala428Val Uncertain significance ★ ⚠ same type
- CTPS2 p.Ala546Thr Uncertain significance ★ ⚠ same type
- CTPS2 p.Arg202Cys Uncertain significance ★ ⚠ same type
- CTPS2 p.Arg217Gln Uncertain significance ★ ⚠ same type
- CTPS2 p.Arg481Gln Uncertain significance ★ ⚠ same type
- CTPS2 p.Arg481Trp 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/ctps2-p-phe59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown