CISH p.Ser173=
c.519C>T · rs61737505 · VCV710598
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, 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 -5.3 |
| Overall | ||
| CADD | 1.648 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
Middle Eastern · 62/6,062 alleles
Filtering AF
0.833%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.828%
Overall
0.724%
11,683/1,613,728 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.02% | 98 |
| Remaining individualsnot grpmax-eligible | 0.89% | 112 |
| Ashkenazi Jewishnot grpmax-eligible | 0.871% | 115 |
| European (non-Finnish) | 0.847% | 118 |
| Admixed American | 0.566% | 177 |
| Finnishnot grpmax-eligible | 0.247% | 406 |
| African / African-American | 0.201% | 497 |
| South Asian | 0.176% | 569 |
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
- CISH
- Protein
- p.Ser173=
- Coding
- c.519C>T
- MANE Select
- NM_145071
- dbSNP
- rs61737505
- Type
- single nucleotide variant
- Location
- chr3:50607865 (GRCh38)
- Gene constraint
- LOEUF 0.956 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.91
- Residue 173
- the 'disordered' region
Similar variants
- CISH p.Arg78Gln Likely benign ★★ same type
- CISH p.Leu223= Benign ★★ same type
- CISH c.20+1222A>G Uncertain significance ★ same type
- CISH c.20+1236G>A Uncertain significance ★ same type
- CISH c.20+1246C>A Uncertain significance ★ same type
- CISH p.Arg107His Uncertain significance ★ ⚠ same type
- CISH p.Arg130Cys Uncertain significance ★ ⚠ same type
- CISH p.Arg139His 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/cish-p-ser173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown