COMP p.Leu754=
c.2262G>A · rs150428337 · VCV194913
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.551%, afr)
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 -0.13 | GERP -2.8, phastCons 0.32 |
| Overall | ||
| CADD | 4.704 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.551%
African / African-American · 413/75,022 alleles
Filtering AF
0.507%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.489%
Overall
0.0279%
450/1,612,236 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.551% | 182 |
| Admixed American | 0.0317% | 3,159 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,468 |
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.Leu754=
- Coding
- c.2262G>A
- MANE Select
- NM_000095
- dbSNP
- rs150428337
- Type
- single nucleotide variant
- Location
- chr19:18782927 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 754
- the 'mediates cell survival and induction of the iap family of survival proteins' region; an α-helix
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-leu754 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown