COMP p.Ala260=
c.780C>G · rs745720934 · VCV1967133
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0017%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.80 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -4 |
| Overall | ||
| CADD | 0.456 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0017%
European (non-Finnish) · 20/1,177,184 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000902%
Overall
0.00144%
21/1,455,006 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0017% | 58,859 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,158 |
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.Ala260=
- Coding
- c.780C>G
- MANE Select
- NM_000095
- dbSNP
- rs745720934
- Type
- single nucleotide variant
- Location
- chr19:18788497 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 260
- a β-strand; a disulfide bond; the egf-like 4 domain
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-p-ala260 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown