CTPS1 p.Leu561=
c.1683C>G · rs2524362153 · VCV2638726
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
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 -0.093 | GERP -4.5, phastCons 0.5 |
| Overall | ||
| CADD | 4.682 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,028 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000137%
2/1,461,864 alleles · very rare
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
- CTPS1
- Protein
- p.Leu561=
- Coding
- c.1683C>G
- MANE Select
- NM_001905
- dbSNP
- rs2524362153
- Type
- single nucleotide variant
- Location
- chr1:41009581 (GRCh38)
- Gene constraint
- LOEUF 0.423 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 91.46 · 7 PDB
Similar variants
- CTPS1 c.1692-1G>C Pathogenic ★★ same type
- CTPS1 c.1095-5T>G Uncertain significance ★★ same type
- CTPS1 p.Ala471Thr Uncertain significance ★★ ⚠ same type
- CTPS1 p.Arg102Trp Uncertain significance ★★ ⚠ same type
- CTPS1 p.Arg294His Uncertain significance ★★ ⚠ same type
- CTPS1 p.Arg376Gln Uncertain significance ★★ ⚠ same type
- CTPS1 p.Arg550Gln Uncertain significance ★★ ⚠ same type
- CTPS1 p.Asn412Ser 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/ctps1-p-leu561 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown