COMP p.Ala218=
c.654G>T · rs749271182 · VCV2964221
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00157%, nfe)
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 -1.2 | GERP -2.7 |
| Overall | ||
| CADD | 7.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00157%
European (non-Finnish) · 18/1,144,730 alleles
Filtering AF
0.000983%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000811%
Overall
0.00117%
18/1,540,938 alleles · very 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
- Protein
- p.Ala218=
- Coding
- c.654G>T
- MANE Select
- NM_000095
- dbSNP
- rs749271182
- Type
- single nucleotide variant
- Location
- chr19:18788700 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 218
- a disulfide bond; the egf-like 3; calcium-binding domain
Similar variants
- COMP p.Ala218Val Uncertain significance ★ ⚠ same residue
- 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
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-ala218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown