ACAN p.Arg308=
c.924C>G · rs117583968 · VCV745735
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.01%, eas)
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 0.49 | GERP 0.79, phastCons 0.99 |
| Overall | ||
| CADD | 10.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.01%
East Asian · 454/44,868 alleles
Filtering AF
0.935%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.905%
Overall
0.0318%
513/1,612,694 alleles · low-frequency
exomes 470/1,460,346 · genomes 43/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.01% | 99 |
| South Asian | 0.0362% | 2,759 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,470 |
| Middle Eastern | 0.0165% | 6,062 |
| European (non-Finnish) | 0.000593% | 168,531 |
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.Arg308=
- Coding
- c.924C>G
- MANE Select
- NM_001369268
- dbSNP
- rs117583968
- Type
- single nucleotide variant
- Location
- chr15:88843521 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 308
- a β-strand; the link 2 domain; the 'g1-b'' region
Similar variants
- ACAN p.Arg308His Uncertain significance ★ ⚠ same residue
- 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
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-arg308 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown