COMP p.Leu16=
c.48C>T · VCV3350924
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.017%, sas)
Conditions
1
COMP-related disorder
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 -2.3 | GERP -2.9 |
| Overall | ||
| CADD | 0.976 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.017%
South Asian · 15/87,996 alleles
Filtering AF
0.0105%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00848%
Overall
0.00106%
17/1,596,300 alleles · ultra-rare
exomes 17/1,443,966 · genomes 0/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.017% | 5,866 |
| European (non-Finnish) | 0.00017% | 586,548 |
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
- Protein
- p.Leu16=
- Coding
- c.48C>T
- MANE Select
- NM_000095
- Type
- single nucleotide variant
- Location
- chr19:18791222 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
Disease context
COMP-related disorder
Similar variants
- COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asp401Asn Pathogenic ★★ same condition
- COMP p.Asp458Gly Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asp507Gly Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asp518His Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Cys484Gly Likely pathogenic ★★ same condition
- COMP p.Gly501Asp Pathogenic/Likely pathogenic ★★ same condition
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-p-leu16 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown