CUBN c.489+35A>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 19.9%, sas) — 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 +35 | near-intronic (+35 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.8 | GERP -2.5 |
| Non-coding constraint | Z -0.69 | 1 kb window · o/e 1.05 · regional · uncalibrated |
| Overall | ||
| CADD | 4.935 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19.9%
South Asian · 17,201/86,456 alleles
Filtering AF
19.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 19.5%
Overall
9.25%
134,371/1,452,092 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 19.9% | 5 |
| Amishnot grpmax-eligible | 15.1% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 11.7% | 9 |
| Middle Eastern | 10.6% | 9 |
| Remaining individualsnot grpmax-eligible | 9.47% | 11 |
| European (non-Finnish) | 9.35% | 11 |
| Finnishnot grpmax-eligible | 9.06% | 11 |
| Admixed American | 4.75% | 21 |
| African / African-American | 2.12% | 47 |
| East Asian | 2.05% | 49 |
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
- CUBN
- Coding
- c.489+35A>C
- MANE Select
- NM_001081
- dbSNP
- rs2273737
- Type
- single nucleotide variant
- Location
- chr10:17123553 (GRCh38)
- Gene constraint
- LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- CUBN c.10033-1G>A Likely pathogenic ★★ same type
- CUBN c.1230+1G>A Pathogenic/Likely pathogenic ★★ same type
- CUBN c.3672+2T>C Likely pathogenic ★★ same type
- CUBN c.3829+1G>A Pathogenic/Likely pathogenic ★★ same type
- CUBN c.4350+2T>C Likely pathogenic ★★ same type
- CUBN c.6821+3A>G Pathogenic/Likely pathogenic ★★ same type
- CUBN c.6822-1G>A Likely pathogenic ★★ same type
- CUBN c.8598+1G>T 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/cubn-c-489-plus-35a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown