COMP p.Ala256=
c.768C>A · rs369897902 · VCV1702394
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0136%, eas)
Conditions
1
connective tissue disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.43 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -4 |
| Overall | ||
| CADD | 14.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0136%
East Asian · 6/44,160 alleles
Filtering AF
0.00587%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00399%
Overall
0.000374%
6/1,602,202 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
- Protein
- p.Ala256=
- Coding
- c.768C>A
- MANE Select
- NM_000095
- dbSNP
- rs369897902
- Type
- single nucleotide variant
- Location
- chr19:18788509 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 256
- a disulfide bond; the egf-like 4 domain
Similar variants
- COMP p.Ala256Thr Uncertain significance ★ same residue
- COMP c.217+4A>G Uncertain significance ★★ same condition
- COMP p.Ser444Cys Uncertain significance ★★ ⚠ same condition
- COMP c.2227+8G>A Benign/Likely benign ★★ same condition
- COMP p.Ala171Thr Benign/Likely benign ★★ same condition
- COMP p.Arg718= Benign/Likely benign ★★ same condition
- COMP p.Asn386Asp Benign/Likely benign ★★ same condition
- COMP p.Asn652= Benign/Likely benign ★★ 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-ala256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown