ACAN c.6946+252A>G
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 62.4%, afr) — 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 +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.11 | GERP -2.5 |
| Overall | ||
| CADD | 1.433 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
62.4%
African / African-American · 25,899/41,478 alleles
Filtering AF
61.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 61.5%
Overall
24.5%
37,252/152,204 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 62.4% | 2 |
| South Asian | 28.1% | 4 |
| Remaining individualsnot grpmax-eligible | 20.6% | 5 |
| Middle Eastern | 18.7% | 5 |
| Admixed American | 14.1% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 12.2% | 8 |
| European (non-Finnish) | 8.74% | 11 |
| East Asian | 6.48% | 15 |
| Amishnot grpmax-eligible | 6.03% | 17 |
| Finnishnot grpmax-eligible | 5.54% | 18 |
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
- ACAN
- Coding
- c.6946+252A>G
- MANE Select
- NM_001369268
- dbSNP
- rs9630453
- Type
- single nucleotide variant
- Location
- chr15:88860691 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
Similar variants
- ACAN c.1733-2A>G Likely pathogenic ★★ same type
- ACAN c.630-13G>A Pathogenic ★★ same type
- ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg236Ter Pathogenic ★★ same type
- ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg394Ter Pathogenic ★★ same type
- ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Asp2419Asn 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/acan-c-6946-plus-252a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown