COMP c.166-9C>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | acceptor -9 | acceptor splice region (-9, within the last 20 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.64 | acceptor loss · deltas |
| Pangolin | Δ0.56 | loss · gain 0.23 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -3.9, phastCons 0.052 |
| Non-coding constraint | Z 3.45 | 1 kb window · o/e 0.73 · regional · uncalibrated |
| Overall | ||
| CADD | 10.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
East Asian · 12/44,858 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.000821%
12/1,461,728 alleles · ultra-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
- COMP
- Coding
- c.166-9C>G
- MANE Select
- NM_000095
- dbSNP
- rs763525913
- Type
- single nucleotide variant
- Location
- chr19:18790622 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
Similar variants
- COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asp273Val Likely pathogenic ★★ same type
- COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same type
- COMP p.Asp349His Pathogenic ★★ 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/comp-c-166-minus-9c-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown