ACAN p.Pro414=
c.1242C>T · rs375758859 · VCV742911
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.3%, 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 -14 | GERP -3.5 |
| Overall | ||
| CADD | 0.229 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.3%
African / African-American · 225/75,064 alleles
Filtering AF
0.268%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.255%
Overall
0.0201%
324/1,613,992 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.3% | 334 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,604 |
| Admixed American | 0.0133% | 7,504 |
| European (non-Finnish) | 0.00509% | 19,665 |
| East Asian | 0.00446% | 22,437 |
| South Asian | 0.0011% | 91,082 |
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
- Protein
- p.Pro414=
- Coding
- c.1242C>T
- MANE Select
- NM_001369268
- dbSNP
- rs375758859
- Type
- single nucleotide variant
- Location
- chr15:88845695 (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-p-pro414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown