COMP c.528+76T>C
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 7.23%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +76 | deep intronic (+76 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.12 | GERP -0.24, phastCons 0.001 |
| Non-coding constraint | Z 6.05 | 1 kb window · o/e 0.64 · regional · uncalibrated |
| Overall | ||
| CADD | 5.034 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.23%
East Asian · 3,174/43,908 alleles
Filtering AF
7.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.93%
Overall
2.38%
37,207/1,560,796 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 7.23% | 14 |
| Finnishnot grpmax-eligible | 4.73% | 21 |
| Ashkenazi Jewishnot grpmax-eligible | 4.52% | 22 |
| Middle Eastern | 3.38% | 30 |
| Remaining individualsnot grpmax-eligible | 2.39% | 42 |
| European (non-Finnish) | 2.31% | 43 |
| South Asian | 1.2% | 84 |
| Admixed American | 0.955% | 105 |
| Amishnot grpmax-eligible | 0.549% | 182 |
| African / African-American | 0.464% | 216 |
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
- Coding
- c.528+76T>C
- MANE Select
- NM_000095
- dbSNP
- rs74798576
- Type
- single nucleotide variant
- Location
- chr19:18789084 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
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-c-528-plus-76t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown