Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.204%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -5.2 |
| Overall | ||
| CADD | 3.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.204%
African / African-American · 153/75,048 alleles
Filtering AF
0.178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.167%
Overall
0.0105%
169/1,614,174 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.204% | 491 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,812 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| Admixed American | 0.00333% | 30,015 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000339% | 295,004 |
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
- CASP9
- Protein
- p.Ser175=
- Coding
- c.525C>T
- MANE Select
- NM_001229
- dbSNP
- rs2308948
- Type
- single nucleotide variant
- Location
- chr1:15507004 (GRCh38)
- Gene constraint
- LOEUF 0.994 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.86 · 13 PDB
- Residue 175
- an α-helix
Similar variants
- CASP9 c.720+9C>T Benign ★★ same type
- CASP9 p.Ala28Val Benign ★★ same type
- CASP9 p.Thr366Asn Benign ★★ same type
- CASP9 p.Ala141Val Uncertain significance ★ ⚠ same type
- CASP9 p.Ala215Thr Uncertain significance ★ ⚠ same type
- CASP9 p.Ala220Val Uncertain significance ★ same type
- CASP9 p.Ala226Ser Uncertain significance ★ ⚠ same type
- CASP9 p.Ala28Thr 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/casp9-p-ser175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown